hMSH2 expression is associated with paclitaxel resistance in ovarian carcinoma, and inhibition of hMSH2 expression in vitro restores paclitaxel sensitivity

Zhang,Jin; Yin,Dongmei; Li,Hongxia

doi:10.3892/or.2014.3430

hMSH2 expression is associated with paclitaxel resistance in ovarian carcinoma, and inhibition of hMSH2 expression in vitro restores paclitaxel sensitivity

Authors:
- Jin Zhang
- Dongmei Yin
- Hongxia Li
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Affiliations: Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Haidian, Beijing 100038, P.R. China, Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Dongcheng, Beijing 100006, P.R. China
Published online on: August 20, 2014 https://doi.org/10.3892/or.2014.3430
Pages: 2199-2206

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Abstract

The objective of the present study was to investigate the association between paclitaxel resistance, gene copy number, and gene expression in ovarian carcinoma, and to restore paclitaxel sensitivity in a paclitaxel-resistant ovarian carcinoma cell line by using hMSH2-targeting siRNA. Paclitaxel-resistant ovarian carcinoma cell lines OC3/TAX300 and OC3/TAX50 and their parental cell lines were analyzed by comparative genomic hybridization, and the expression levels of hMSH2 in ovarian carcinoma cell lines and tissues were determined. An siRNA targeted to hMSH2 mRNA was used to transfect a paclitaxel-resistant cell line. We assessed the morphological features, proliferation, and susceptibility to apoptosis of the transfected cells after paclitaxel treatment. Chromosome 2p21 (gene locus of hMSH2) was amplified in OC3/TAX300 cells. hMSH2 was overexpressed in 93.9 and 47.6% of paclitaxel-treated and untreated ovarian carcinoma tissue samples (P=0.0001), respectively. hMSH2 was overexpressed in 93.3 and 54.2% of low-differentiated and moderate-to-highly differentiated ovarian carcinoma tissue samples (P=0.0008), respectively. hMSH2 expression was inhibited in the OC3/TAX300 cells transfected with hMSH2 siRNA. hMSH2 siRNA increased paclitaxel sensitivity, inhibited OC3/TAX300 cell proliferation (G2/M arrest), and increased susceptibility to apoptosis. hMSH2 expression was upregulated in ovarian carcinoma cell lines and tissues after paclitaxel treatment. hMSH2 overexpression is related to paclitaxel resistance and poor prognosis. Inhibition of hMSH2 expression in vitro restores paclitaxel sensitivity in paclitaxel‑resistant ovarian carcinoma cell lines and indicates a new direction in adjuvant therapy for ovarian carcinoma.

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