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Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells.

ABSTRACT: Ovarian cancer is the leading cause of mortality among all gynecological malignancies. Drug resistance is a cause of ovarian cancer recurrence and low rate of overall survival. There is a requirement for more effective treatment approaches. Cucurbitacin B (CuB) is an antineoplastic agent derived from traditional Chinese medicinal herbs. Its activity against paclitaxel-resistant human ovarian cancer cells has, however, not yet been established. The purpose of the present study was to investigate the effect and mechanism of CuB on human paclitaxel-resistant ovarian cancer A2780/Taxol cells. Cell viability was evaluated by a cell counting assay, while cell cycle arrest and apoptosis were assessed by microscopy and flow cytometry, and proteins associated with apoptotic pathways and drug resistance were evaluated by western blotting. The present results demonstrated that CuB exerts dose- and time-dependent cytotoxicity against the ovarian cancer A2780 cell line, with half-maximal inhibitory concentration (IC50) values 0.48, 0.25 and 0.21 µM following 24, 48 and 72 h of incubation, respectively. Compared with its sensitive counterpart, A2780, paclitaxel-resistant A2780/Taxol cells had almost identical IC50 values. Cell cycle analysis demonstrated that treatment with CuB may induce cell cycle arrest at the G2/M phase of the cell cycle in the two cell lines. As revealed by Annexin V/propidium iodide-labeled flow cytometry and Hoechst 33258 staining, CuB-induced apoptosis was accompanied by activation of caspase-3 and downregulation of B-cell lymphoma-2. Western blotting demonstrated that CuB may enhance the expression of p53 and p21 in the two cell lines. CuB may also downregulate the expression of P-glycoprotein. These results indicate that CuB may exert a therapeutic effect on paclitaxel-resistant human ovarian cancer.

SUBMITTER: Qu Y

PROVIDER: S-EPMC5494940 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells.

Qu Yingchun Y Cong Peifang P Lin Chengjiang C Deng Yihui Y Li-Ling Jesse J Zhang Meixia M

Oncology letters 20170510 1

Ovarian cancer is the leading cause of mortality among all gynecological malignancies. Drug resistance is a cause of ovarian cancer recurrence and low rate of overall survival. There is a requirement for more effective treatment approaches. Cucurbitacin B (CuB) is an antineoplastic agent derived from traditional Chinese medicinal herbs. Its activity against paclitaxel-resistant human ovarian cancer cells has, however, not yet been established. The purpose of the present study was to investigate ...[more]

PMID: 28693146

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Project description:Background and Aims: Ovarian carcinoma (OC) is one of the most lethal malignant tumors with a high reoccurrence and chemoresistance. The key mechanism relationship with chemoresistance in ovarian carcinoma is still unclear. The existence of cancer stem cells involves in chemoresistance and reoccurrence in OC. The objective of this study was to investigate the expression, suppression of malignant properties and reversal of paclitaxel resistance inhibiting RNA-binding protein Musashi-1 with siRNA in ovarian cancer cells. Methods: The expression of MSI-1 was analyzed in 39 normal ovarian epithelia tissues, 92 serous cystadenomas, 68 borderline serous cystadenomas, and 97 serous cystadenocarcinomas by immunohistochemistry. pLKO.1-MSI-1-siRNA expression vector was transfected into ovarian carcinoma cell line A2780 and its paclitaxel-resistant cell subline A2780/Taxol. The roles of MSI-1 in proliferation, apoptosis, migration and invasion were explored by cell proliferation analysis, Caspase 3 activity assay, wound healing assay, migration and matrigel invasion assay, respectively. Western Blotting and Real-time quantitative PCR were conducted to detect the expression of MSI-1 and the ERK signaling pathway. Reversal of paclitaxel resistance assay was used to evaluate the role of MSI-1 in paclitaxel resistance of OC cells. Finally, therapeutic effects of MSI-1 inhibition were investigated the xenogratfs of SCID mice in vivo of the paclitacel-resistant. Results: MSI-1 is overexpressed and associated with an unfavorable prognosis in OC patients. Knockdown of MSI-1 by small interfering RNA (siRNA) inhibits proliferation, promotes apoptosis, and reduces migration and invasion of cancer cells. Moreover, MSI-1 expression inhibition reverses paclitaxel-resistance in OC cells. We further display that MSI-1 effectively protects OC cells from paclitaxel-induced apoptosis by increasing the expression of p-Bcl-2 through ERK signaling pathway activation. In vivo, MSI-1 siRNA clearly showed a strong effect on tumor growth inhibition and paclitaxel-resistance reversal. Conclusions: These findings suggest that MSI-1 overexpression is associated with the prognosis of OC patients, and knockdown of MSI-1 can suppress malignant properties and reverse paclitaxel-resistance in OC cells. MSI-1 maybe act as a potential prognostic indicator and a therapeutic target in OC.

Dataset Information

Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells.

Publications

Inhibition of paclitaxel resistance and apoptosis induction by cucurbitacin B in ovarian carcinoma cells.

Similar Datasets

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