Abstract Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer,
which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in
cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical
treatment of seizure disorders. In addition, this drug may display its effects through regulation
of noncoding RNAs controlling gene expression. The aim of the present study was the
investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the
relation of the H19 levels with apoptosis and cisplatin resistance. Briefly, treatment with VPA
not only led to significant increase in apoptosis rate, but also increased the cisplatin sensitivity
of A2780/CP cells. We found that following VPA treatment, the expression of H19 and EZH2
decreased, but the expression of p21 and PTEN increased significantly. To investigate the
involvement of H19 in VPA-induced apoptosis and cisplatin sensitivity, H19 was inhibited by
a specific siRNA. Our results demonstrate that H19 knockdown by siRNA induced apoptosis
and sensitized the A2780/CP cells to cisplatin-induced cytotoxicity. These data indicated that
VPA negatively regulates the expression of H19 in ovarian cancer cells, which subsequently
leads to apoptosis induction, cell proliferation inhibition, and overwhelming to cisplatin
resistance. The implication of H19→EZH2→p21/PTEN pathway by VPA treatment suggests
