Investigation of the effect of oxidative stress on NRF3, POMP and autophagıc gene expressions in gastric cancer

Gastric cancer is a malignant tumor that is seen in the fifth place worldwide and in the third place in cancer-related deaths. Oxidative stress is a state of imbalance between oxidants and antioxidants in the cell. Increased reactive oxygen derivatives (ROS) in the cell contribute to the development of cancer by causing cellular damage.Suppression of oxidative stress by antioxidants is extremely important for maintaining cellular homeostasis. Caffeic acid phenethyl ester (CAPE), one of the main components of propolis, is a flavonoid compound with anti-cancer and antioxidant effects. NRF1, NRF2 and NRF3, which belong to the Cap'n collar (CNC) protein family, are transcription factors that are activated against cellular stress factors. The physiological roles of NRF3 are not yet clear. It is known that NRF3 is highly expressed in cancer cells. Proteosome maturation protein (POMP) is responsible for the biogenesis of the 20S proteosome by acting as a chaperone. Autophagy; It is a self-destruct mechanism activated as a result of stress factors such as nutrient deficiency, hypoxia and oxidative stress. In this thesis, it was aimed to suppress oxidative stress by applying CAPE, an antioxidant, to AGS and MKN-45 gastric cancer cells, in which hydrogen peroxide-mediated oxidative stress conditions were created for the first time, and to examine NRF3, POMP and Beclin-1 gene expressions in both treatment groups.The cytotoxicity of Hydrogen Peroxide on cells was determined by MTT analysis. AGS and MKN-45 cells were cultured under appropriate conditions, and then hydrogen peroxide and CAPE, an antioxidant, were applied to the cells. NRF3, POMP and Beclin-1 expressions were investigated by real-time polymerase chain reaction method in treated AGS and MKN-45 cells. Our findings showed that NRF3 gene expressions decreased and POMP and Beclin-1 gene expressions increased in both cell lines under oxidative stress conditions. After suppression of oxidative stress with antioxidant CAPE, NRF3 gene expressions increased in both cell lines, while Beclin-1 gene expressions decreased. POMP gene expressions, on the other hand, increased under oxidative stress conditions. The results suggest that NRF3, which is known to be highly expressed in gastric cancer, may also play a role as an oncogene in gastric cancer under oxidative stress conditions and that the increased expression of POMP, which is known to be directly induced by NRF3, under stress conditions may activate apoptotic mechanisms in gastric cancer cells. However, it also suggests that oxidative stress conditions may increase gastric cancer survival by activating autophagy mechanisms, increasing Beclin-1 gene expressions in gastric cancer cells.