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 dosedependent 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 topaclitaxel.
 Keywords: Esomeprazole, V-ATPase, Apoptosis, Ovarian cancer, Taxol, Sensitivity
Highlights
Ovarian cancer accounts for the highest mortality among gynecological tumors, second only to cervical cancer and uterine body cancer
The purpose of this study was to investigate the effect of inhibition of V-ATPase on the apoptosis and sensitivity of ovarian cancer cells to paclitaxel
The protein expression of V-ATPase in drugresistant cells was markedly higher than that in sensitive cells, and the combined treatment with esomeprazole and paclitaxel significantly reduced the expression of V-ATPase protein in cells, when compared with paclitaxel monotherapy group
Summary
Ovarian cancer accounts for the highest mortality among gynecological tumors, second only to cervical cancer and uterine body cancer. The purpose of this study was to investigate the effect of inhibition of V-ATPase on the apoptosis and sensitivity of ovarian cancer cells to paclitaxel. Antibody against V-ATPase was obtained from Santa Cruz Company, United States, while BCA protein quantitative assay kit was purchased from Biyuntian Institute of Technology. The protein from each treatment was subjected to SDSpolyacrylamide gel electrophoresis, followed by transfer of the bands to polyvinylidene membrane, blocking of non-specific binding, and incubation with primary antibodies for Bcl-2, the Bcl-xl, P-gp and V-ATPase. This was followed by incubation with secondary antibody at room temperature overnight. All statistical analyses were carried out with SPSS 21.0 software
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