ovarian cancer

Cervical, breast, and ovarian cancers exhibit significant incidence and fatality rates, necessitating di verse approaches for effective cancer cell eradication while preserving normal cells. The aim of this study is to explore the in vitro apoptosis-inducing properties of hydroalcoholic extracts from Cyperus rotundus’ (C. rotundus) leaf using human gynecological cancer cell lines. In this experimental study, Hydroalcoholic extracts were prepared from the leaf of C. rotundus using ethanol, methanol, and ethyl acetate. These extracts were applied to MCF-7, HeLa, OVCAR-3, and Vero cell lines at concentrations of 3.125, 6.25, 12.5, and 25 g/ml. MTT test, assessing inhibition of proliferation at 50% (IC50), was employed to evaluate each extract’s ability to inhibit cell proliferation. Subsequently, apoptosis-related gene and protein regulation were examined using reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the methanolic extract contained hexadecanoic acid and dodecanoic acid. The ethanolic extract was found to have norspermidine and desulphosinigrin. Additionally, the ethyl acetate extract included vitamin E, 1-heptatriacotanol, lupeol, betulin, stigmasterol, and stearic acid. The HeLa treatment group with 6.25 μg/ml of ethyl acetate extract, MCF-7, and OVCAR-3 cells with 3.125 μg/ ml of methanol extract treatment group exhibited the most significant growth inhibition in the MTT assay. Further analysis of these treatment groups revealed that the transcription and translation of BAX, Caspase-3, Caspase-8, and Caspase-9 increased overall, whereas Bcl-2 decreased in all cell lines. Hydroalcoholic extracts from C. rotundus’ leaf may enhance the apoptosis of cancer cells by modulat ing the transcription, translation, and post-translation of proteins, with minimal impact on the growth and survival of non-cancerous cells.

Breast and ovarian cancers are prevalent among women, prompting researchers to focus on developing new pharmaceutical agents and innovative drug delivery systems aimed at enhancing treatment efficacy while minimizing side effects. Steviol glycosides offer a promising approach to cancer treatment due to their broad anticancer activity, low toxicity, selective targeting of cancer cells, and potential to enhance chemotherapy efficacy.

This study explores the potential of steviol glycoside, a natural compound derived from the Stevia rebaudiana plant, as an anticancer agent targeting breast (MCF-7) and ovarian (A2780) cancer cell lines.

MCF-7 and A2780 cells were cultured under standard conditions and treated with varying concentrations of steviol glycoside (0, 10, 20, 30, 40, and 50 µM) over different time points (24, 48, and 72 hours). Cell viability was assessed using the MTT assay, and the expression of apoptotic and anti-apoptotic genes was evaluated. Statistical analyses were performed using a t-test, with P-values calculated based on a significance threshold of 0.05. Graphs were generated using GraphPad Prism software.

The inhibitory concentration 50% (IC50) values for MCF-7 cells were 30 μM, 24 μM, and 22 μM at 24, 48, and 72 hours, respectively. For A2780 cells, the corresponding IC50 values were 24 μM, 20 μM, and 19 μM at the same time points. The fold change in Bax and Bad gene expression increased with rising concentrations of steviol glycoside. At concentrations above 20 μM, this increase became statistically significant (P < 0.001). Conversely, Bcl-2 gene expression exhibited a statistically significant decrease (P < 0.001) at these concentrations.

The findings highlight the therapeutic potential of steviol glycoside in treating breast and ovarian cancers, emphasizing the need for deeper investigation into its molecular pathways to fully understand its mechanisms. Despite its promise, significant challenges exist in translating laboratory results into clinical applications. Key obstacles include establishing appropriate dosing, assessing interactions with other medications, and conducting comprehensive trials to ensure safety and efficacy. Acknowledging these limitations enhances transparency and underscores the necessity for additional research to progress toward human trials.

This study focused on macrocyclic diterpenes derived from Euphorbia, particularly myrsinanes, and their potential in cytotoxic and combination treatments for resistant cancer cells. We examine premyrsinanes isolated from Euphorbia malleata and explore their cytotoxic properties.

Euphorbia malleata was collected from Taragh-Roud, Natanz, Iran. The semi-polar chloroform/acetone extract was chromatographed and fractionated using a large silica column. Fractions containing diterpene resonances were selected based on 1H-NMR spectra and were further subjected to smaller silica or Sephadex columns, followed by a recycling HPLC system. The isolated compounds were identified through 1D and 2D-NMR experiments and mass spectrometry. The cytotoxicity of the isolated compounds was assessed using the MTT assay against A2780 wild and A2780 cisplatin-resistant (R-CIS) cells, both in mono and combination treatments with cisplatin.

Using a Waters 616 HPLC pump and a YMC prep silica column, we successfully isolated two new premyrsinane diterpenes (Malleatin A and Malleatin B) alongside two known compounds (beta-sitosterol and loliolide). Malleatin A exhibited cytotoxicity against A2780 wild and A2780 R-CIS cells, with an IC50 range of 50 - 65 μM in the MTT assay. While cisplatin demonstrated significant cytotoxic effects on the A2780 wild cell line, it was ineffective against the A2780 R-CIS cells due to their resistance. However, the combination therapy of Malleatin A and cisplatin exhibited a synergistic effect, significantly increasing the mortality rate of the resistant cells compared to monotherapy. The Combination Index (CI) of 0.58 indicates effective synergy, and the Dose Reduction Index (DRI) of 3.65 suggests a favorable reduction in the dosage of cisplatin needed, potentially reducing its associated side effects.

Radical surgery is the most effective treatment in ovarian cancer advanced stages, making reliable biomarkers essential for enhancing diagnostic accuracy. Human Epididymis 4 (HE4) is considered a dependable diagnostic biomarker; its diagnostic precision is outweighed by Cancer Antigen 125 (CA 125). The present study was conducted with aim to evaluate immunoassay of CA 125 and HE4 during progression-free survival (PFS) period in ovarian cancer patients.

This observational analytical study was designed to answer whether the measurement of the tumour biomarkers, CA125 and HE4 protein, can aid in monitoring ovarian cancer patients in the postoperative period or detect the progression-free survival period.  Seventy-three ovarian serous adenocarcinoma patients undergoing debulking surgery were grouped according to ovarian cancer grade, FIGO staging and progression free survival period during adjuvant therapy, each three months comparison of the serum level of CA125 and HE4 consequently. The study continued for about four years with various periods for each patient.

During the PFS period, the lowest biomarkers mean of CA125 was 17.1 U/ml during the ninth month after surgery; while the mean for HE4 was 28.4 pg /ml during the sixth month. Both biomarkers increased during the PFS periods, with HE4 increasing in the ninth month and CA125 in the 12th month, indicating that HE4 increased before CA125. There is an increase in the mean serum level of both HE4 and CA125 with decrease in histopathological differentiation and increased FIGO staging, before surgery, two weeks after surgery, PFS period, and after PFS period.

The study found that the immunoassay of CA 125 and HE4 in ovarian cancer tissues can be used to monitor the effect of surgery and to evaluate the patient's in PFS period.

Ovarian Low-grade serous carcinoma (LGSC), a type of epithelial ovarian tumor, is often diagnosed in the advanced stage. Treatment involves surgery and chemotherapy. In advanced stages (3 and 4), removing all tumoral implants with both the uterus and ovaries (debunking surgery) is the first surgical goal. We presented a case of a 38-year-old woman who became pregnant three years after being diagnosed with LGSOC at stage 3c. We resected all tumoral implants, and decision was made to preserve the uterus for her since the patient wanted to be pregnant. The patient underwent surgery, then followed by a standard chemotherapy regime. During the three years of follow-up, there were no signs of tumor return; she decided to get pregnant by egg donation through an in vitro fertilization (IVF) procedure. A cesarean section was done, and the twin infants were born in good condition and with good APGAR scores.

Granulosa cell tumor (GCT) is a sex cord-stromal rare malignancy; and is associated with infertility. Extracellular vesicles (EVs) are small secreted vesicles containing proteins, mRNA, and miRNA, therefore modulating signaling pathways potentially in recipient cells and in this way, they can help cancer spread through intercellular communication. In this research, the capability of ovarian cancer-derived EVs for inducing proliferation and metastasis in GCs is investigated. In the experimental study, EVs were isolated by ultracentrifugation from A2780 human ovarian cancer cell-conditioned. Mouse GCs were mechanically isolated from 8 female mice. ovarian cancer-derived EVs were then added to the GCs (experimental groups: untreated GCs (control group), GCs treated with concentrations of 10, 25, and 50 μg/ml), and cell viability, migration, apoptosis, and estrogen hormone measurements were assessed by MTT, scratch assay, propidium iodide (PI) staining, annexin-V-FITC/PI and ELISA assay respectively. Gene's expression of Amh, Foxl2, Gdf-9, and Igf-1r were determined using real-time polymerase chain reaction (PCR). GCs treated with ovarian cancer EVs indicate an increase in cell viability compared to the control cells (P<0.05). Also, ovarian cancer EVs showed an increase in the migration potency. The other results this experimental study showed that ovarian cancer EVs increase in the estrogen secretion level (P<0.001) and reduce the apoptosis of GCs compared to the control group. It is further showed that EVs isolated from ovarian cancer (A2780 cell line) can induce the RNA expression level of several genes in recipient GCs, such as Amh, Foxl2, and Igf-1r (P<0.01, P<0.001), respectively, while the RNA expression level of Gdf-9 gene was decreased in comparison with the control. To sum up, the research here provides a novel insight into the role of ovarian cancer EVs in proliferation and metastasis in GCs and prevention of infertility caused by granulosa cancer.

Antiemetic that prevents nausea and vomiting for ovarian cancer patients during chemotherapy, have major effects on the quality of life and adherence to patients’ treatment. This study aims to study the effectiveness of antiemetic in improving ovarian cancer patient’s quality of life using Functional Living Index Emesis (FLIE) scale.

A cross-sectional study, data collection by total sampling method from 31 patients who received chemotherapy with emetogenic level 5 and were given antiemetic as Chemotherapy Induced Nausea and Vomiting (CINV) in the obstetrics and gynecology ward and one daycare service room at tertiary referral hospital X in Padang city, West Sumatra Indonesia. FLIE score was measured at 3 different measurement times, before chemotherapy administration, acute phase, and delayed phase.

The FLIE score before chemotherapy administration was 6.94, acute phase 6.09, and delayed phase 4.88.  The highest FLIE score is 7 which indicates no nausea or vomiting, while the lower FLIE score suggests the more severe nausea and vomiting experienced by the patient. Bivariate test with a Kruskal-Wallis in the acute phase obtained a value of P>0.05, implying there is no difference in the average FLIE score of patients in the acute phase and in the delayed phase obtained a value of p≤0.05 which means there is a difference in the average FLIE score in the delayed phase among patients based on the antiemetic given.

The antiemetic given has not been effective in maintaining a good patient quality of life, especially in the delayed phase.

Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death. Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA). The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged. The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.

Ovarian cancer, particularly aggressive subtypes like SK-OV-3, remains a significant challenge due to limited treatment options, necessitating the development of more effective therapeutic strategies. Aluminum oxide nanoparticle (Al2O3NPs) have demonstrated potential in cancer therapy because of their unique properties, including enhanced drug delivery and cytotoxic effects. This study investigates the synergistic anticancer effects of aluminum nanoparticles combined with doxorubicin on SK-OV-3 ovarian cancer cells. The effectiveness of the combination treatment was assessed by evaluating cell viability using the MTT assay. Oxidative stress was quantified by measuring reactive oxygen species (ROS) levels with the DCFH reagent, while lipid peroxidation (LPO) was analyzed by detecting malondialdehyde (MDA) levels. The antioxidant capacity was measured by assessing glutathione (GSH) levels. The results indicated that the combination of Al2O3NPs and doxorubicin significantly reduced SK-OV-3 cell viability, suggesting potent anticancer effects. Additionally, the treatment induced oxidative stress, as evidenced by increased ROS production, elevated MDA levels, and decreased GSH levels. These findings demonstrate that aluminum nanoparticles, in combination with doxorubicin, exert a synergistic anticancer effect by promoting oxidative stress and inhibiting the proliferation of SK-OV-3 cells. These findings underscore the potential of Al2O3NPs as an effective therapeutic modality in ovarian cancer treatment, particularly for aggressive subtypes like SK-OV-3.

High-intensity focused ultrasound (HIFU) represents a therapeutic medical procedure that operates by inducing ablation and mechanical disruption. Despite its established efficacy, its potential impact on tumor chemotherapy remains uncertain. Long noncoding RNA (lncRNA) MAFA-AS1 facilitated cancer cell proliferation and fostering drug resistance, but the precise significance and functional implications of MAFA-AS1 in the context of ovarian cancer (OC) remain largely unexplored. The objective of this experiment is to further investigate the potential of HIFU in inhibiting the chemotherapy resistance mechanism of OC.

Five types of human ovarian cancer cells were employed in this study. There were four different groups, namely MAFA-AS1 siRNA, si-NC, pcDNA3.1-HIF-1 (hypoxia-inducible factor-1), and pcDNA3.1-control. Quantitative real-time PCR, cell proliferation assay, apoptosis assay, western blot assay, subcellular fractionation, aerobic glycolysis analysis, RNA immunoprecipitation (RIP), and luciferase reporter assay were conducted for experimentation and validation.

Significant upregulation of MAFA-AS1 in OC cells was observed. Through loss-of-function experiments based on HIFU, we unraveled its oncogenic functions in OC. MAFA-AS1 was discovered to bind to HIF-1 mRNA, thereby enhancing its expressed stability. Further investigations revealed an interaction between MAFA-AS1 and fat mass and obesity-associated protein (FTO), positively modulating HIF-1 mRNA stability in an FTO-dependent manner. Importantly, MAFA-AS1 exerts its effects on OC by acting through HIF-1.

The study underscores the role of MAFA-AS1 in promoting aerobic glycolysis and chemical resistance in OC by up-regulating HIF-1 expression, suggesting that targeting MAFA-AS1 holds promise as a therapeutic strategy for OC patients undergoing chemotherapy.

Ovarian cancer (OC) occurs when aberrant cells proliferate and form a tumor, which is known as ovarian cancer, mostly of unknown causes. It is crucial to investigate the effect of biotherapies like Bevacizumab (Avastin) and chemotherapy on the gene expression of PD1 and PDL1 in ovarian cancer patients to understand the molecular dynamics of therapeutic responses. The present study was conducted with aim to investigate the effect of adjuvant therapy on the expression of a gene on the exterior of T-cells “Programmed cell death 1” (PD1) and on tumor cells “Programmed cell death ligand 1” (PDL1) in OC patients.

The study included 24 OC patients who were divided into three groups: Group 1 (G1) with 1-6 doses of Avastin, Group 2 (G2) with >6 doses of Avastin, and Group 3 (G3) receiving chemotherapy, along with 8 healthy controls. Gene expression of PD1 and PDL1 was analyzed using Real-Time PCR.

PD1 and PDL1 did not show significant differences between the study groups (P=0.62 and P=0.153, respectively). Additionally, there was a strong correlation between PD1 and PDL1 expression in all groups (P=0.0012, P=0.006, and P=0.010 for G1, G2, and G3, respectively). The gene PD1 was downregulated in patients compared to controls (P=0.637, P=0.730, P=0.697, and P=1.004 for G1, G2, G3, and control, respectively). Similarly, the gene PDL1 was downregulated in patients (P=0.340, P=0.209, P=0.477, and P=1.000 for G1, G2, G3, and control, respectively).

The expression of PD1 and PDL1 and their correlation in ovarian cancer patients may indeed have a significant impact on evaluating therapeutic responses in these patients. Understanding the gene expression profiles of PD1 and PDL1 could provide valuable insights into the immune response and potential treatment outcomes for ovarian cancer.

Cisplatin resistance presents a considerable hurdle in the treatment of ovarian cancer, significantly impacting patient outcomes and limiting the effectiveness of chemotherapy. This study employs advanced bioinformatics techniques-including RNA sequencing (RNA-seq), DNA sequencing (DNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq)-to elucidate the molecular mechanisms underlying this resistance, with a particular focus on the long non-coding RNA (lncRNA) LINC02381. Our findings reveal that LINC02381 is significantly upregulated in ovarian cancer cells exhibiting resistance to cisplatin, suggesting its pivotal role in mediating this phenomenon. We further demonstrate that cytokines, particularly interleukin-12 (IL-12), secreted by immune cells within the tumor microenvironment, activate the Wnt signaling pathway. This activation leads to the binding of the transcription factor TCF7 to the promoter region of LINC02381, resulting in enhanced expression of this lncRNA. Notably, this interaction establishes a positive feedback loop in which LINC02381 not only promotes its own expression but also amplifies Wnt signaling activity. This cascade ultimately drives the upregulation of ATP-binding cassette (ABC) transporters, which are crucial for the efflux of cisplatin from cancer cells. Thus, the drug's intracellular concentration is reduced, and cell survival under chemotherapy pressure is facilitated. These insights uncover a novel mechanism of cisplatin resistance driven by the IL-12/Wnt/TCF7/LINC02381 axis, highlighting the complex interplay between immune signaling and drug resistance in ovarian cancer. Our findings suggest that targeting this regulatory pathway may offer promising therapeutic strategies to overcome chemotherapy resistance, paving the way for improved treatment outcomes in patients with ovarian cancer. Future research should focus on validating these mechanisms and exploring potential interventions that disrupt this feedback loop.

The new plan of using molecular targeted agents in combination with cytotoxic drugs may represent a promising strategy to increase the efficacy of chemotherapy. Hence, we examined whether α2β1 integrin-specific inhibitor, BTT-3033, could modulate the susceptibility of OVCAR3 and SKOV3 ovarian cancer cells to paclitaxel (PTX).

Experimental approach: 

Ovarian cancer cell lines were treated with BTT-3033 and different concentrations of PTX. To determine the mechanisms involved in the PTX/BTT-3033 combination-induced cell death, cell viability, apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and caspase-3 activity were evaluated.

Both BTT-3033 (≥ 1 μM) and PTX (≥ 0.01 μM) suppressed the proliferation of OVCAR3 and SKOV3 cells in a concentration-related manner. Pretreatment with BTT-3033 (1 μM), followed by PTX-induced synergistic antiproliferative effects, decreased the IC50 values of PTX from 0.45 to 0.03 μM in OVCAR3 and 0.35 to 0.02 μM in SKOV3 cells. All of the coefficients of drug interaction for various PTX and BTT-3033 combinations were found to be less than 1. Moreover, PTX/BTT-3033 combination induced more apoptotic cells (from 4.2% to 87.0% in OVCAR3 and 2.4% to 88.5% in SKOV3) than PTX alone. Combination therapy also decreased MMP and increased the caspase-3 activity. Additionally, we found that the PTX/BTT-3033 combination enhanced ROS production in OVCAR3 and SKOV3 cells.

Conclusion and implications: 

BTT-3033 has demonstrated the ability to enhance the susceptibility of ovarian cancer cells to PTX by inducing MMP loss, ROS production, and mitochondrial apoptosis, therefore this combination therapy might represent a promising strategy for ovarian cancer treatment.

Synchronized endometrial and ovarian cancer (SEOC) is a condition in which there is both primary endometrial and primary ovarian cancer at the same time in a patient. These tumors have a better prognosis than metastatic ones. Most of them are diagnosed in the early stages and are low-grade tumors. So differentiation of this kind of rare tumor from others is essential. No adjuvant chemotherapy seems to be reasonable in cases with low-grade tumors both in endometrioid and non-endometrioid types. High-grades tumors have been described less, but, in some studies, genetic mutations were found in these tumors, which have been the basis of targeted therapy after surgery.

In this report, two rare non-endometrioid types of SEOC cases are discussed. The first case is a low-grade papillary serous carcinoma of the ovary and uterus endometrium. In contrast, the second case is a clear cell carcinoma of the ovary and endometrioid adenocarcinoma of the uterus. We also review the literature in this field.

We conclude that in these cases, chemotherapy with routine regimens does not seem to be helpful in early stages with low-grade tumors. Also, in high-grade tumors, targeted therapy may be more effective than adjuvant chemotherapy.

surgery (CRS) and neoadjuvant chemotherapy (NACT) are recommended for advanced ovarian cancer (aOC) treatment. This study aimed to investigate the therapy-induced genomic changes and immune microenvironment alteration in patients with aOC.

The microarray data of ovarian cancer samples from naïve or treated patients were collected from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) between samples were screened. Consensus clustering was conducted to explore the molecular subtypes of ovarian cancer samples. The correlation between tertiary lymphoid structure (TLS) signatures with the molecular subtypes was subject to Gene set variation analysis (GSVA). The prognostic signature of aOC was constructed using machine learning based on lasso-cox regression. Finally, immune infiltration analysis was performed for immune landscape evaluation in aOC.

Totally 28 DEGs were found between the control and treatment groups. Enrichment analysis indicated the association of these genes with the immune changes. Moreover, the cluster 1/2 (C1/C2) of ovarian cancer were identified, and the C1 subtype had higher enrichment of TLS-related biomarkers. Moreover, 15 genes were revealed as independent factors for the prediction of ovarian cancer prognosis. Immune infiltration levels were significantly higher in the C1 subtype, which indicated the distinct immune landscape between the two molecular subtypes of ovarian cancer.

The NACT and CRS induced genomic changes were related to immune response in aOC. The findings of our study might deepen our understanding of the TLS-related signature and immune pattern in aOC patients.

 Ovarian cancer ranks among the most prevalent gynecologic cancers in women with the majority of patients experiencing a recurrent type and developing treatment resistance. Resistance to chemotherapy drugs has been observed to trigger epithelial-mesenchymal transition (EMT), which leads to the acquisition of metastatic properties. Thus, targeting the molecular mechanism of EMT may lead to novel interventions against metastatic disease. In this research, the suppressive impacts of fucoxanthin, as a natural compound, were examined on cell migration and expression of key EMT-related markers in ovarian cancer cells which were sensitive and resistant to cisplatin.

 To determine the non-toxic concentrations of fucoxanthin for migration assay, the MTT assay was conducted. To assess the anti-migratory capacity of fucoxanthin in ovarian cancer cells which were sensitive and resistant to cisplatin, a wound-healing migration test was done in the presence of non-toxic concentrations of fucoxanthin. RT-qPCR was utilized to examine the impact of fucoxanthin on the mRNA expression of E-cadherin, vimentin and α- SMA (as EMT-related markers) in ovarian cancer cells.

 Fucoxanthin at concentrations of (1 and 2.5 μM) downregulated the expression of α–SMA in cisplatin-resistant ovarian cancer cells and inhibited migration in ovarian cancer cell lines.

Fucoxanthin exhibited remarkable efficacy in inhibiting migration in in ovarian cancer cells which were sensitive and resistant to cisplatin. However, more research is required to ascertain the clinical advantages linked to utilizing fucoxanthin in the treatment of cisplatin-resistant ovarian cancers.

There is an increase in the incidence of breast and gynecologic cancers in Iran during the last three decades. Literature is inadequate about the Years of Life Lost (YLL) attributed to these cancers in Iran.

Mortality data due to these cancers amongst females aged >20 yr from 2004 to 2019 was acquired from “Electronic Death Registry System”, Fars Province, Iran. Using local health centers’ databases and national census reports from 1996 to 2016, the age-standardized incidence rate (ASR) per 100,000 people were estimated. YLLs were calculated using the WHO’s 2015 “YLL template”.

During 2004–2019, 1886 and 829 deaths occurred due to breast and gynecologic cancers, respectively. The ASR due to breast and gynecologic cancers showed a significant increasing trend (P<0.001 for each). The total YLL due to breast, cervical/uterine/vaginal/vulvar, and ovary cancers’ deaths in the 16-year period were 33,077, 7,172 and 6,584 yr, respectively. The highest YLLs were observed in 50-59-year-old females, followed by 40-49- and 60-69-year-old females. The 16- year trend of YLL rate due to premature mortality in breast cancer, ovary cancer and cervix cancer was increasing: annual percent change (APC) was 7.6% (95% CI: 5.5-9.7, P<0.001), 19.0% (95% CI: 12.2-26.1, P<0.001) and 9.2% (95% CI: -9.2 to 31.3, P>0.05, respectively.

Mortality rate and YLLs due to breast and gynecologic cancers have been increased in southern Iran during the last twenty years. Early detection programs and allocating treatments at early stages should be prioritized.

The significant functional role of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer, has been shown in various studies. In this study, we aimed to investigate the abnormal expression of hsa_circ_0008285 and its role in ovarian cancer pathogenesis. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot methods were used to detect the expression of hsa_circ_0008285 and some target genes in ovarian cancer tissues and related cell lines. To determine the functional roles of hsa_circ_0008285 in ovarian cancer, cell proliferation, apoptosis, and cell invasion assays were performed. Bioinformatics (Target scan, circ intractome) and luciferase reporter analyses were used to predict target genes.

In the present study, we first found that hsa_circ_0008285 was up regulated in ovarian cancer tissues and related cell lines. Bioinformatics, experimental data, and luciferase reporter analysis data showed miR-211-5p is a direct target of hsa_circ_0008285, while SIRT-1 is a direct target of miR-211-5p. Overexpression of hsa_circ_0008285 in cancer cells increased the expression of SIRT-1 and progression of cancer cells. Based on these results, inhibition of hsa_circ_0008285 expression could cause upregulation of miR-211-5p and down regulation of SIRT-1 and inhibited the proliferation and invasion of ovarian cancer cells.

The results of the present study revealed that hsa_circ_0008285 suppressed ovarian cancer progression by regulating miR-211-5p expression to inhibit SIRT-1 expression.