Investigating the effects of combining metformin and simvastatin on ovarian cancer cells and on the regulation of miRNA-mRNA network

Description :

Ovarian Cancer (OC) is the most lethal gynecological malignancy and is ranked among the five most common death-causing cancers in women worldwide (Mahdian-Shakib et al., 2016). If OC is diagnosed at an early stage, the 5-year overall survival (OS) reaches around 90%. However, the latter decreases to 25% when OC is diagnosed in advanced stages (III/IV). In fact, this is what happens in most cases due to its non-specific signs and symptoms, which is why OC is described as the “silent killer” (Matulonis et al., 2016). These indicate the need to enhance the understanding in tumor biology, ultimately, to improve treatment strategies. In this attempt, researchers have brought an old drug into the oncologic circle that has shown to be an effective strategy in battling cancer: Metformin. Metformin is a biguanide, commonly used for type II diabetes. Currently, it is the center of attention as a potential anti-cancer drug, and researchers all around the world are investigating its mechanism of action. In general, metformin restores the metabolic homeostasis, reprogrammed aberrantly in cancer cells, which is recognized as a hallmark of cancer and as an essential entity for cancer cell survival and proliferation (Hanahan and Weinberg, 2011). Among other drugs also brought into cancer research are statins. Statins inhibit 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme a Reductase enzyme (HMG-CoAR) that catalyzes the conversion of HMG-CoA to mevalonic acid. It is currently used extensively for treating hypercholesterolemia and preventing cardiovascular diseases. Based on the fact that an increase in lipid synthesis is observed as an alteration in cancer metabolic reprogramming, statins are now under the oncologic spotlight. Both metformin and statins are metabolic altering medications that might have synergistic activity together and/or with chemotherapeutic medications in proliferation, cell cycle, programmed death and several other aspects of ovarian cancer cells. If this hypothesis is proven correct, this in vitro study will provide a novel approach to the treatment of ovarian cancer, which is the most lethal gynecological malignancy and where improving response rates is an urgent clinical issue.