The effect of metformin on the progression of non-small cell lung cancer with diabetes mellitus: A review of studies between 2015 and 2017

Non-small cell lung cancer (NSCLC), the most common type of lung cancers, has the highest mortality rate among cancers. Diabetes mellitus is one of the most common comorbidity in NSCLC. It seems necessary to study an effective new therapeutic regimen due to the anticarcinogenicity effects of metformin, as a comman antidiabetic drug, for the treatment of NSCLC in patients with diabetes mellitus simultaneously. The aim of this study was to provide the latest evidences and mechanisms of action of metformin in relation to the anticancer effects in patients with NSCLC and diabetes, based on studies in 2015-2017. This review study investigated anticancer effects of metformin specially non-small cell lung cancer by utilizing the latest electronic articles in Journals in databases "Science Direct, Springer, and OVID" as well as information search databases "Web of Science, and Scopus". Recently, numerous studies about the relationship between metformin and reduced mortality rate of cancers performed, while some studies did not show any relationship. Metformin, as a mTOR (Mammalian Target of Rapamycin) inhibitor, exerts its anticancer effects by activation of the AMPK pathway. Also, Metformin can prevent cancer cell mitosis by inducing activation of the immune system and decreased signaling of the growth factors. It also increases IL-2, TNFα and IFNγ, inhibition of TIL (Tumor-Infiltrating Lymphocyte) apoptosis and inhibition of GTPase. Suppression of MicroRNA222 due to metformin administration leads to increase p27 and p57 and as a result it impairs cell cycle of tumor cells. Metformin by several different mechanism may lead to a reduction in risk or increasing of NSCLC improvement. In clinical, Metformin could use as an adjuvant with radiotherapy and chemotherapy.