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 effectsof various chemotherapeutic agents are limited in patients with platinum resistance. Therefore, developing new anticancer drugs that canimprove the effect of currently used cytostatics is critical. The current study investigated the effects of valproic acid (VPA) alone and incombination with cisplatin on ovarian cancer cells.Methods: In this experimental study, the human ovarian cancer cell lines (A۲۷۸۰-S and A۲۷۸۰-CP) were grown in RPMI-۱۶۴۰ medium inappropriate culture conditions. The cells were treated with various concentrations of cisplatin (۰.۱۵-۴۰۰ μg/mL) or VPA (۱۰-۲۰۰۰ μg/mL)and were incubated for ۲۴, ۴۸, and ۷۲ hours. Moreover, A۲۷۸۰ cells were co-treated with different concentrations of cisplatin and VPA for۴۸ hours. Afterward, cell viability was investigated using MTT assay. GraphPad Prism statistical software was used for the data analysis andANOVA 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, cotreatmentof the A۲۷۸۰ cells with cisplatin and VPA resulted in a significantly greater inhibition of cell viability compared to the treatmentwith either agent alone.Conclusion: Overall, it can be argued that VPA does not only cause inhibition of proliferation and induction of apoptosis in ovarian cancercells but also helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistantcells. VPA may therefore be used to treat cancer in the future.