Effect of valproic acid on cisplatin-resistant ovarian cancer cell lines

Background and aims: Platinum resistance has been one of the most important problems in the management of ovarian cancer. The effects of various chemotherapeutic agents are limited in patients with platinum resistance. Therefore, developing new anticancer drugs that can improve the effect of currently used cytostatics is critical. The current study investigated the effects of valproic acid (VPA) alone and in combination with cisplatin on ovarian cancer cells. Methods: In this experimental study, the human ovarian cancer cell lines (A2780-S and A2780-CP) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated with various concentrations of cisplatin (0.15-400 µg/mL) or VPA (10-2000 µg/mL) and were incubated for 24, 48, and 72 hours. Moreover, A2780 cells were co-treated with different concentrations of cisplatin and VPA for 48 hours. Afterward, cell viability was investigated using MTT assay. GraphPad Prism statistical software was used for the data analysis and ANOVA and Duncan’s test were conducted. Results: A dose- and time-dependent reduction was observed in cell viability following the treatment with cisplatin or VPA. Moreover, cotreatment of the A2780 cells with cisplatin and VPA resulted in a significantly greater inhibition of cell viability compared to the treatment with either agent alone. Conclusion: Overall, it can be argued that VPA does not only cause inhibition of proliferation and induction of apoptosis in ovarian cancer cells but also helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistant cells. VPA may therefore be used to treat cancer in the future. Keywords: Ovarian cancer, Cisplatin, Valproic acid, Platinum resistance, Antiproliferative effec