The combination of sorafenib and lansoprazole the role of hepatocellular carcinoma cells on in vitro analysis of synergistic anticancer effects

Hepatocellular Carcinoma (HCC), the most common type of liver tumor, ranks first in cancer-related deaths worldwide. Sorafenib, the only chemotherapeutic drug used in the treatment of HCC, imposes restrictions on the applied treatments. For this reason, stud-ies are being carried out on plant-derived substances or drug combinations together with the currently available agent used in cancer treatment. In this thesis, the synergistic anti-cancer effects of drug combinations were investigated in HepG2 cells, a HCC Line, in order to increase the effect of Sorafenib with the combination and to develop new treatment methods in the treatment of HCC. In this study, the effects of the existing agent Sorafenib and Lansoprazole, an antiulcer drug from a proton pump inhibitor group, on cell viability were investigated by the MTT method after being exposed to HepG2 cells individually and in combination for a specified dose and period of time. In order to determine its genotoxic effects, it was subjected to the Comet test. Thus, the damage left by the combination of Sorafenib and Lansoprazole in HepG2 cell DNA was examined. In addition, a real-time polymerase chain reaction (PCR) test was performed to detect changes in mRNA levels in apoptosis-related genes. Based on the MTT results, it was observed that the combination dose of Sorafenib and Lansoprazole had a more significant effect on reducing cell viability compared to single doses. When PCR results were examined, changes in Bax, Bcl-2, Caspase-3 and Tnf-ɑ protein levels were deter-mined. It was determined that combined groups induced apoptotic mechanism com-pared to single groups. In line with this thesis, the cytotoxic, synergistic and anti-cancer effects of the combination of Sorafenib and Lansoprazole on HepG2 cells were investi-gated in vitro and it was determined that Sorafenib and Lansoprazole showed synergis-tic effects.