Studying the molecular effect of melatonin on sensitivity of a SW480 colon cancer cell line to etoposide

Abstract

The resistance of cancer cells to the apoptotic effects of chemotherapy drugs can lead to the failure of chemotherapy, which is one of the most serious challenges in the treatment of colorectal cancer. In recent years, in order to overcome this challenge, much attention has been paid to natural compounds with the ability to increase DNA damage and apoptosis. The aim is to use these compounds to increase the efficiency of chemotherapy drugs in inducing apoptosis. Among these compounds is melatonin and this study focused on it. Methods Colon cancer cell line SW480 was used in this study. Laboratory tests including MTT ,Annexin V/PI, western blot, ELISA, DCFH-DA and qRT- PCR were used to investigate the effects of melatonin, and the combination of etoposide and melatonin on viability, apoptosis, ROS levels, levels of DNA damage markers (γH2AX and (8-OXO dG ), expression of cytokines (IL-6 and IL-10), COX2 expression and miR155 expression in SW480 cells. Results The results of this study showed that the combination of melatonin and etoposide can significantly increase the levels of ROS, 8-OXO-dG, γH2AX and apoptosis in SW480 cells (P < 0.05). The rate of apoptosis in the cells treated with the combination of melatonin and etoposide was 32.66%, while it was 8.06% in the control group. In addition, the combination of melatonin and etoposide can decrease the expression of IL6, IL10, COX2 and miR155 in SW480 cells (P < 0.05). All these effects are weaker if melatonin or etoposide are used alone.