The role of melatoni̇n mediated by TRPV1 channels in cisplatinapplied pancrease and stomach cancer cells

Gastric and pancreatic cancers are frequently seen in the World and they have high mortality rates. Cisplatin is a neoplastic agent that damages the DNA and it is the preferred treatment of many types of cancer. In the current thesis, the possible effects of the combined use of cisplatin and melatonin on gastric and pancreatic cancer cells via TRPV1 channels were investigated. For this reason, gastric and pancreatic cells were divided into 7 groups as control, cisplatin, cisplatin+capsazepine, cisplatin+melatonin, cisplatin+melatonin+capsazepine, melatonin and melatonin+capsazepine. Capsaicin was also used for TRPV1 channel activation. Intracellular calcium ion level, reactive oxygen radicals, mitochondrial depolarization, caspase 3 and caspase 9 enzyme activation and apoptosis levels were measured in the cells. When the results of calcium signal analysis in gastric and pancreatic cancer cells were examined, cisplatin, cisplatin+melatonin and melatonin groups were found to be higher compared to the control group (p˂0.001). When the cisplatin group and cisplatin+melatonin groups are compared, the cytosolic free calcium level in the cisplatin+melatonin group was higher (p˂0.001). However, when apoptosis, reactive oxygen species, mitochondrial depolarization levels, and caspase 3 and caspase 9 enzyme activations in gastric and pancreatic cancer cells were examined, cisplatin, cisplatin+melatonin and melatonin groups were higher than the control group (p˂0.001), cisplatin group and cisplatin+ When the melatonin group was compared, it was observed that the cisplatin+melatonin group was higher (p˂0.05 and p˂0.001) In sum, in the related analyzes, it was observed that the values in the groups that used the TRPV1 channel blocker is capsazepine, cisplatin and melatonin separately or together, were lower (p˂0.05 and p˂0.001) compared to similar groups that did not use capsazepine. As a result; It was determined that the combined use of cisplatin + melatonin compared to the cisplatin group caused more apoptotic effects in cancer cells and this activity was also mediated by TRPV1 channels. Keywords: Pancreatic Cancer, Gastric Cancer, Apoptosis, Oxidative Stress, TRPV1