Pitavastatinin Sisplatin ile Birlikte Antikanserojen Etkilerinin İnsan Serviks Kanser Hücrelerinde Araştırılması

Abstract

Cervical cancer is one of the most widespread malignant tumors in women around the world today. Pitavastatin is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor widely used to treat hypercholesterolemia and in recent studies focuses that its anticancer effect. In this thesis study, it was aimed to determine the possible anticancer effects of pitavastatin on cervical cancer cells (HeLa) under in vitro conditions. For this reason, cell apoptosis and cell cycle analyses were performed in flow cytometry. Genotoxic effects were assessed with standard Comet assay and formamidopyrimidine glycosylase (fpg)-modified Comet assay. Intracellular reactive reactive oxygen species (ROS) levels were measured in HeLa cells. Also, the effects of apoptosis related proteins were evaluated by caspase 3/8/9 multiple assay kit and Western blotting. According to results, in cell cycle analysis, an increased proportion of sub G1 cells was monitored and induced apoptosis in HeLa cells. Pitavastatin was shown to cause the generation of ROS in high concentrations. DNA damage increased significantly above the 20 µM concentration compared to the control. It was observed that pitavastatin increased the expression of active caspase-9 and -3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) in HeLa cells. In conclusion, it was shown that the combined effect of pitavastatin with cisplatin was stronger than its solo effect and pitavastatin may be a potential candidate for use in cervical cancer treatment research.