Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of V-ATPase

Yasong Chi, Ruiqin Yue, Yanru Lv, Wei Liao, Ruchang Yin

Department of Gynecology, Liaocheng Second People's Hospital, Linqing, PR China;

For correspondence:- Ruchang Yin Email: brc91c@163.com

Accepted: 27 July 2020 Published: 31 August 2020

Citation: Chi Y, Yue R, Lv Y, Liao W, Yin R. Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of V-ATPase. Trop J Pharm Res 2020; 19(8):1585-1590 doi: 10.4314/tjpr.v19i8.3

© 2020 The authors.
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Abstract

Purpose: To determine the effect of esomeprazole on apoptosis of ovarian cancer cells and their sensitivity to paclitaxel, and the underlying mechanism.

Methods: Human ovarian paclitaxel-resistant cancer cells were cultured in vitro, and treated with esomeprazole at doses of 50, 100 and 250 mol/L. Cell proliferation was determined using MTT assay. Paclitaxel-resistant cells were divided into control group, esomeprazole group, paclitaxel group, and esomeprazole + taxol group. Western blot was employed for the assay of protein levels of bcl-2, Bcl-xl, P-gp and V-ATPase, while BCECF-AM method was employed to determine changes in intracellular pH.

Results: Esomeprazole significantly inhibited the proliferation of paclitaxel-resistant cells in a dose-dependent manner. The half-maximal inhibitory concentration (IC₅₀) value of esomeprazole + paclitaxel was significantly low, when compared with those of the other treatments (p < 0.05). Apoptosis was significantly higher in esomeprazole + paclitaxel group than in any other treatment group (p < 0.05). The expressions of Bcl-2 and P-gp in esomeprazole + paclitaxel group decreased significantly, relative to the corresponding values for other groups, while protein expression of bcl-xl was markedly increased. The intracellular pH value of esomeprazole + paclitaxel group was significantly lower than those for other treatment groups (p < 0.05).

Conclusion: Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of V-ATPase, and restores the sensitivity of ovarian cancer cells to paclitaxel by inhibiting their proliferation and apoptosis. This revelation may explain patients’ resistance to paclitaxel.

Keywords: Esomeprazole, V-ATPase, Apoptosis, Ovarian cancer, Taxol, Sensitivity