Metabolome profile comparison of cisplatin sensitive and resistant in ovarian epithelial cells by magnetic resonance spectroscopy spectroscopy

Epithelial ovarian carcinoma is considered to be the most lethal gynecological malignancy in women and accounts for more than 85% of ovarian carcinomas. The chemotherapeutical treatment of choice is cisplatin. However, long-term use of this drug mostly results in drug resistance phenomenon. Metabolomics, is a highly resourceful technique, which acts promising in monitoring of tumor growth. Proton nuclear magnetic resonance spectroscopy (1H-NMR) is a non-invasive and high reproducible technique used in metabolomics. In the present investigation, we tried to find biochemical pathways and their metabolic alterations in epithelial cells of ovarian carcinoma and study the mechanism involved in cisplatin drug resistance.
The cell lines A2780 and A2780CP were prepared. Methanol-chloroform-water extraction was performed.The hydrophilic layer were collected separately and cell1H-NMR spectroscopy were applied on a Bruker spectrometer operating at 400 MHz. After processing the data, outlier metabolites were identified and their biochemical pathways were worked out by Metaboanalyst and Human Metabolome Database.
In the present study, the main altered metabolites were; fucose, sorbitol, mannitol, mannose, rhamnose, glycerol, galactonite, alpha lactose, myo-inositol and melibiose. The biochemical pathway enrichment analysis showed that galactose, fructose and mannose metabolism was the most prominent altered pathways.
Our results disclose that cisplatin resistance results from alteration in carbohydrates metabolites and their pathways. However, further study is needed to confirm these findings