AN EVALUATION OF MELATONIN INFLUENCE ON SENSITIVITY TO CISPLATIN THROUGH EXPRESSION OF SURVIVIN, XIAP, CASPASE-3, AND AKT GENES IN OVCAR3 OVARIAN CANCER CELLS

Background & Aims: Ovarian cancer is the seventh most common cancer and the fifth most common
cause of death among women worldwide. Therefore, it is necessary to find new drugs that increase the
effectiveness of chemotherapy drugs and the possibility of using them in lower doses, which leads to a
reduction in side effects. The aim of this study was to evaluate the effect of melatonin on the expression
of XIAP, Survivin, AKT, and caspase 3 genes in order to increase cisplatin sensitivity in cultured
OVCAR3 cells.
Materials & Methods: In this study, OVCAR3 cells with different concentrations of melatonin (0.001,
0.312, 0.625, 1.25, 2.5, 5,10 μM) and different concentrations of cisplatin (0.001, 0.937, 1.875, 3.75,
7.5, 15 μM) were cultivated at 24, 48, and 72 hours. Then, cytotoxicity was assessed by MTT assay.
Real-time PCR test was performed to evaluate the relative gene expression level of XIAP, Survivin,
AKT, and caspase 3 genes in control, melatonin, cisplatin, and a combination of melatonin and cisplatin
groups.
Results: The results of this study showed that melatonin inhibits the proliferation of cultured OVCAR3
cells based on a dose and time-dependent mechanism. The results of analysis showed that there is a
significant increase in the gene expression level of caspase 3 regarding melatonin and melatonincisplatin
groups. Also, the expression of Survivin apoptosis inhibitor gene in melatonin-cisplatin
combination group decreased (borderline difference). There were no significant changes in tested groups
regarding relative gene expression of Xiap and Akt.
Conclusion: The findings of this study show that OVCAR3 cells became more sensitive to cisplatin in
the presence of melatonin. It can be used to manage patients with ovarian cancer.