Research of everolimus on ovary clear cell carcinoma cell line on PTEN/mTOR/VEGF pathway with apoptosis

Ovary's clear cell cancers are among the low differential and treatment-resistant cancers. mTOR forms the junction of many stimulant paths in the cell and it stimulates cell proliferation and angiogenesis through VEGF. PTEN, a tumor suppressor and it has the key role in cell cycle. It does the inhibition of PI3K. Everolimus, which is mTOR inhibitor, is a derivative of rapamycin which has a effect of antiangiogenic and antiproliferative. In our study, it is aimed to show the evaluate the cytotoxic, apoptotic and genomic effects of everolimus on ES-2 cell line, on PTEN/mTOR/VEGFA path and to research the effect of taxol, which is a currently used standard treatment element. Treatment with taxol only for 24h incubation at 500nm dose resulted in the low viability percentage (50.3%) while a same percentage (48.1%) was observed after treatment with the very low dose (10nM) taxol and everolimus combination for the same incubation duration. Treatment with 5 nM taxol and 10 nM everolimus combination for the 48h incubation duration resulted low apoptosis percentage (27%) and low viability percentage (46.7%) (p<0.05). After treatment of everolimus and taxol combination VEGFA mRNA and PTEN mRNA level decreased (p<0.05) and mTOR mRNA level unchanged. It further shows that use of everolimus and taxol combination leads to a further increase in this effect. In conclusion, our study draws attention to the possible clinical effectiveness of use of Everolimus together with chemotherapeutic agents with high cytotoxicity due to the opportunity to attain suitable apoptotic effect with reduced dose in cancer treatment targeting PTEN/mTOR/VEGFA pathway.