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

2020 ◽  
Vol 19 (8) ◽  
pp. 1585-1590
Author(s):  
Yasong Chi ◽  
Ruiqin Yue ◽  
Yanru Lv ◽  
Wei Liao ◽  
Ruchang Yin
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ph Value ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Acidic Microenvironment ◽  
Paclitaxel Group ◽  
Resistant Cells

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

Knockdown of Rab25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo

Pathology ◽  
2006 ◽  
Vol 38 (6) ◽  
pp. 561-567 ◽  
Author(s):  
Fan Yang ◽  
Xin Xiao-Yan ◽  
Chen Bi-Liang ◽  
Ma Xiangdong
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

Picropodophyllin inhibits epithelial ovarian cancer cells in vitro and in vivo

2013 ◽  
Vol 435 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Xiaosheng Lu ◽  
Ledan Wang ◽  
Jie Mei ◽  
Xin Wang ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

scholarly journals Metformin inhibits the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination

2020 ◽  
Author(s):  
Xiaojia Min ◽  
Tingting Zhang ◽  
Ying Lin ◽  
Bo Wang ◽  
Kean Zhu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cells ◽  
Related Factors ◽  
P53 Signaling ◽  
P53 Signaling Pathway ◽  
Resistant Cells

Ovarian cancer is the most lethal diseases among women. The chemo-resistance has been a big challenge for the cancer treatment. It has been reported that metformin may inhibit ovarian cancer and is able to impede the development of drug resistance, but the molecular mechanisms remain elusive. In this study, we explored the molecular roles of metformin in Parkin expression and p53 ubiquitination in chemo-resistant ovarian cancer cells. Firstly, ovarian cancer and chemo-resistant ovarian cancer cells were selected for determining the expression of Parkin, p53, and p53 signaling pathway-related factors. Then the cell proliferation and viability after loss- and gain-of-function assays were measured. Besides, immunoprecipitation (IP) was used to determine the interactions between Parkin and p53, and the ubiquitination level of p53 was measured using in vitro ubiquitination assay. Finally, the degradation of p53 proteasome regulated by Parkin was monitored using the MG132 proteasome inhibitor. We found that metformin significantly inhibited the growth of ovarian cancer parental cells and chemo-resistant cells, and metformin promoted Parkin expression in chemo-resistant cells. Further, up-regulated Parkin expression promoted the ubiquitination and degradation of p53, and metformin inhibited the expression of p53 to suppress the proliferation of chemo-resistant ovarian cancer cells. Mechanistically, metformin could inhibit the growth of ovarian cancer cells by promoting the Parkin-induced p53 ubiquitination. Altogether, our study demonstrated an inhibitory role of metformin in the growth of chemo-resistant cancer cells through promoting the Parkin-induced p53 ubiquitination, which provides a novel mechanism of metformin for treating ovarian cancer.

scholarly journals Puerarin induces platinum-resistant epithelial ovarian cancer cell apoptosis by targeting SIRT1

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110407
Author(s):  
Jianxiu Duan ◽  
Mingyuan Yin ◽  
Yaqin Shao ◽  
Jiao Zheng ◽  
Shengdan Nie
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Sirtuin 1 ◽  
Nuclear Accumulation ◽  
Ovarian Cancer Cells ◽  
Platinum Resistant

Objective Previous investigations indicated the anticancer activity of puerarin. The current study aimed to evaluate the effect and molecular mechanisms of puerarin in chemotherapy-resistant ovarian cancer cells. Methods We examined the effects of puerarin in platinum-resistant epithelial ovarian cancer cells in vitro and in vivo. We also analyzed the molecular mechanism underlying Wnt/β-catenin inhibition and sirtuin 1 (SIRT1) regulation following puerarin treatment. Results Our study demonstrated that puerarin effectively inhibited cell growth in vitro and in vivo by increasing apoptosis in ovarian cancer cells. More importantly, puerarin sensitized cisplatin-resistant ovarian cancer cells to chemotherapy. Puerarin treatment decreased SIRT1 expression, which attenuated the nuclear accumulation of β-catenin to inhibit Wnt/β-catenin signaling. In addition, SIRT1 overexpression diminished the effects of puerarin treatment on cisplatin-resistant ovarian cancer cells. Further analysis supported SIRT1/β-catenin expression as a candidate biomarker for the disease progression of epithelial ovarian cancer. Conclusions Puerarin increased the apoptosis of platinum-resistant ovarian cancer cells. The mechanism is partly related to the downregulation of SIRT1 and subsequent inhibition of Wnt/β-catenin signaling.

Overexpression of miR-138-5p Sensitizes Taxol-Resistant Epithelial Ovarian Cancer Cells through Targeting Cyclin-Dependent Kinase 6

2021 ◽  
pp. 1-9
Author(s):  
Man Liang ◽  
Qin Li ◽  
Shuai Shi ◽  
Ya-ning Tian ◽  
Yanhong Feng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Luciferase Assay ◽  
Ovarian Cancer Cells ◽  
Cyclin Dependent Kinase ◽  
Cancer Tissues ◽  
Resistant Cells

<b><i>Background:</i></b> Ovarian cancer, one of the most malignant diseases in female, is associated with poor diagnosis and low 5-year survival rate. Taxol is a widely used chemotherapeutic drug for the treatment of ovarian cancer by targeting the microtubules of the mitotic spindle to induce cancer cell death. However, with the widespread clinical applications of Taxol, a large fraction of ovarian cancer patients developed drug resistance. <b><i>Results:</i></b> Here, we report miR-138-5p is significantly downregulated in epithelial ovarian cancer tissues compared with their matched normal ovarian tissues. Overexpression of miR-138-5p effectively sensitized ovarian cancer cells to Taxol. By establishing Taxol-resistant cell line from the epithelial ovarian cancer cell line, HO-8910, we found miR-138-5p was significantly downregulated in Taxol-resistant cells. Furthermore, overexpression of miR-138-5p dramatically overcame the chemoresistance of Taxol-resistant cells. Intriguingly, bioinformatic analysis indicated miR-138-5p had putative binding sites for cyclin-dependent kinase 6 (CDK6). This negative regulation was further verified from epithelial ovarian cancer tissues. Luciferase assay demonstrated miR-138-5p could directly bind to 3′UTR of CDK6. Importantly, silencing CDK6 expression by siRNA successfully increased the sensitivity of both parental and Taxol-resistant ovarian cancer cells. Finally, rescue experiments clearly elucidated restoration of CDK6 in miR-138-5p-overexpressing ovarian cancer cells successfully recovered the Taxol resistance. <b><i>Conclusion:</i></b> In summary, these findings suggest important molecular mechanisms for the miR-138-5p-mediated Taxol sensitivity of ovarian cancer via directly targeting CDK6, suggesting miR-138-5p is an effective therapeutic target for the noncoding RNA-based anti-chemoresistance treatment.

scholarly journals CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro

2014 ◽  
Vol 35 (2) ◽  
pp. 340-348 ◽  
Author(s):  
ZHUANGYAN ZHU ◽  
YAQIN MU ◽  
CAIXIA QI ◽  
JIAN WANG ◽  
GUOPING XI ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells
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