Effect of Vincristine on apoptosis and autophagy in gastric cancer under hypoxic conditions

Cancer is a multifactorial and aggressive disease that causes many deaths in the world. Stomach cancer is the fourth most common cause of death in the world. In the course of the disease, death mechanisms such as apoptosis and autophagy function largely. Vincristine, on the other hand, is a chemotherapeutic drug that binds to tubulin dimers, causing cancer cells to go to apoptosis. However, Vincristine also protects cancer cells from apoptosis, allowing them to go into autophagy, making cancer even more aggressive in later stages of cancer. In this study, the effects of Vincristine on autophagy under hypoxic conditions are shown for the first time and it is aimed to show the effects of drug use on gastric cancer cell lines and to understand cellular behavior. For this purpose, AGS cells which is p53 mutant and less aggressive MKN45 cells were cultured under appropriate conditions. After treatment with hypoxia and Vincristine, Bax and Bcl-2 genes which in apoptosis, Beclin-1 and LC3-II genes which in autophagy, and HIF-1α and VEGF genes involved in hypoxia, the success of Vincristine used in treating cancer cells have been observed. As a result of various analyzes, it has been observed that Vincristine induces autophagy and causes asidic vasicular organel formation in gastric cancer. In both cell lines, an increase in Beclin-1 and LC3-II expressions was observed compared to control, whereas decrease in pro-apoptotic Bax gene and increase in anti-apoptotic Bcl-2 gene were observed in only AGS cell line. An increase in Bax and Bcl-2 genes was observed in MKN45 cells. It was found that VEGF expression increased in both cell lines but HIF-1α increased in AGS cells and decreased in MKN45 cells. Hypoxia conditions were increased in AGS cells except VEGF, while VEGF, Bax and Beclin-1 genes were increased and HIF-1α, Bcl-2 and LC3-II genes decreased in MKN45 cells. In cases where hypoxia and Vincristine were combinated, expression of all genes were increased in AGS cells and expression of all genes were increased except VEGF was observed in MKN45 cells. As a result, Vincristine was found to induce autophagy in the less aggressive MKN45 cell line compared to the AGS cell line under hypoxic conditions.