ERp57‑small interfering RNA silencing can enhance the sensitivity of drug‑resistant human ovarian cancer cells to paclitaxel

Li,Shuo; Zhao,Xiaoyun; Chang,Shijie; Li,Yanqiu; Guo,Min; Guan,Yifu

doi:10.3892/ijo.2018.4628

ERp57‑small interfering RNA silencing can enhance the sensitivity of drug‑resistant human ovarian cancer cells to paclitaxel

Authors:
- Shuo Li
- Xiaoyun Zhao
- Shijie Chang
- Yanqiu Li
- Min Guo
- Yifu Guan
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Affiliations: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110122, P.R. China, Department of Microbiology and Cell Biology, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P.R. China, Department of Biomedical Engineering, China Medical University, Shenyang, Liaoning 110122, P.R. China
Published online on: November 7, 2018 https://doi.org/10.3892/ijo.2018.4628
Pages: 249-260

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Abstract

ERp57 has been identified to be associated with the chemoresistance of human ovarian cancer. However, its biological roles in the chemoresistance phenotype remain unclear. In the present study, the association of ERp57 with paclitaxel‑resistant cellular behavior was investigated and the sensitivity enhancement of chemoresistant human ovarian cancer cells to paclitaxel was examined using ERp57‑small interfering (si)RNA silencing. Cell viability, cell proliferation, cell apoptosis and cell migration were detected using an MTT assay, clonogenic assay, flow cytometry analysis and transwell assay. Furthermore, mRNA expression levels of ERp57 and protein expression levels of ERp57, STAT3, phosphorylated STAT3, PCNA, nucelolin, TUBB3, P-gp, vimentin, Bcl-2, Bax, Bcl-xl, p53, MMP1, MMP2 and MMP9 of paclitaxel-sensitive human SKOV3 ovarian cancer cells were compared with paclitaxel-resistant counterpart SKOV3/tax using the real-time PCR and western blot analysis. ERp57 was highly expressed in the paclitaxel‑resistant SKOV3/tax cells, and experimental results concluded that the paclitaxel‑resistance phenotype was due primarily to the activation of the STAT3 signaling pathway. ERp57 overexpression by lentiviral particle infection decreased the sensitivity of SKOV3 cells to paclitaxel. Furthermore, ERp57‑siRNA silencing restored paclitaxel sensitivity of SKOV3/tax cells. Notably, the IC50 value of ERp57‑siRNA silenced SKOV3/tax cells was reduced to the original level and colony survival was significantly decreased in comparison with that of SKOV3/tax cells. Additionally, co‑treatment of ERp57‑siRNA silencing and paclitaxel could inhibit the STAT3 signaling pathway and downregulate the expression levels of downstream proteins. Notably, ERp57‑siRNA and 100 nM paclitaxel co‑treatment downregulated Bcl‑2, Bcl‑xl, MMP2, MMP9, TUBB3 and P‑gp expression levels and upregulated the expression of Bax protein. Furthermore, co‑treatment promoted change of the isoform of p53 to p53/p47. Bioinformatics analyses supported the experimental observations that ERp57 was associated with drug resistance in ovarian cancer. The present study implies that ERp57 is a potential therapeutic target for the treatment of paclitaxel‑resistant human ovarian cancer.

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