Abstract
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.
Highlights
Ovarian cancer is one of the most prevalent cancers worldwide and the first leading cause of death as a reproductive system cancer among women [1]
Our results showed a dose-dependent decrease in cell viability, suggesting that A2780-CP cells were more sensitive to valproic acid (VPA) treatment (IC50 values = 1000, 400, 275 μg/mL) than A2780-S cells (IC50 values= 1200, 650, 425 μg/mL) in different time points (Figure 2, Table 1)
The investigation of A2780-S cells under different concentrations of cisplatin and VPA for 48 hours showed a more significant reduction of cell viability in combination therapy compared to monotherapy
Summary
Ovarian cancer is one of the most prevalent cancers worldwide and the first leading cause of death as a reproductive system cancer among women [1]. Despite its high therapeutic potential, cisplatin is not widely used to treat ovarian cancer due partly to reduced intracellular drug accumulation, increased platinum-DNA adduct repair, and enhanced platinum-DNA damage tolerance that lead to intense side effects and development of cisplatin resistance in cancer cells [2,6]. The current study investigated the effects of valproic acid (VPA) alone and in combination with cisplatin on ovarian cancer cells. Conclusion: Overall, it can be argued that VPA does cause inhibition of proliferation and induction of apoptosis in ovarian cancer cells and helps to enhance the antiproliferative effects of cisplatin and results in the increased susceptibility to cisplatin in resistant cells.
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