Anti-cancer Effects of Ketoprofen on the Expression of HE4 Gene and Viability of the A2780 Human Ovarian Cancer Cell Line

Abstract

Background: Ovarian cancer is the second leading cause of death in Iran compared with other gynecological diseases. Considering the role of cyclooxygenase (COX) enzymes and prostaglandin E2 production in tumor lesions, nonsteroidal anti-inflammatory drugs (NSAIDs) show antitumor properties by inhibiting COX. Furthermore, some compounds can serve as non-selective inhibitors of COX (such as ketoprofen) and prevent cancer development. Human epididymis protein 4 (HE4) is one of the most sensitive tumor markers known in the study of the disease of ovarian epithelial cancer. The expression of HE4 increases in different types of ovarian cancer. Objectives: The aim of this study was to determine the anti-cancer effects of ketoprofen on the viability of ovarian cancer cells and expression of HE4 gene. Methods: To calculate half-maximal inhibitory concentration (IC50), A2780S cells were treated with different concentrations of ketoprofen for 24 hours, then the cells were incubated with appropriate concentrations of IC50 for 24, 48, and 72 hours. Real-time polymerase chain reaction (PCR) was used to measure changes caused by the effect of drugs on HE4 gene expression and analyzed by the 2-ΔΔCT method. Results: The IC50 level of ketoprofen for 24 hours was 583.7 μM. According to real-time PCR results, treatment of cells with ketoprofen reduced HE4 expression. Conclusions: HE4 gene expression decreased in cells treated with ketoprofen compared with the cells in the control group, which proves the anti-cancer activity of ketoprofen and a reduction in the viability of ovarian cancer cells.