Esomeprazole improves the acidic microenvironment of epithelial ovarian cancer by inhibiting the expression of VATPase

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, Sensitivit

Propofol affects the biological behavior of ovarian cancer SKOV3 cells via ERK1/2-MMP-2/9 signaling pathway

Purpose: To investigate the effect of propofol on the biological behavior of ovarian cancer SKOV3 cells, and the mechanism of action involved. Methods: SKOV3 cells cultured in vitro were randomly divided into control group, fat emulsion group, low-dose propofol group (LDPG, 25 μmol/L), medium-dose propofol group (MDPG) (50 μmol/L) and high-dose propofol group (HDPG) (100 μmol/L). Apoptosis was determined by flow cytometry, while Transwell assay was used to measure the migration and invasion abilities of the cells. The protein levels of ERK1/2, MMP-2, MMP-9 were assayed with Western blotting. Moreover, the cells were transfected with siERK, and the regulatory effect of propofol on ERK1/2-MMP-2/9 signaling pathway was determined. Results: Apoptosis in HDPG was significantly reduced, relative to MDPG, while migration and invasion were enhanced, relative to MDPG (p < 0.05). Moreover, MMP-2, ERK1/2, and MMP-9 proteins were significantly higher in MDPG and HDPG than in control, fat emulsion and LDPGs (p < 0.05), and were upregulated in HDPGs, relative to MDPG (p < 0.05). In contrast, propofol did not up-regulate these proteins in siRNA-treated cells. Conclusion: Propofol enhances the migration, proliferation, and invasive ability SKOV3 cells, and upregulates the expressions of MMP-2, ERK1/2, and MMP-9 in these cells, via a mechanism related to the activation of ERK1/2-MMP-2/9 signaling route. These properties provide novel leads for the development of new drugs for ovarian cancer Keywords: Propofol, ERK1/2-MMP-2/9 signal route, Ovarian cancer, Biological behavio