hMMS2基因对结肠癌细胞耐药逆转的影响

doi:10.3724/SP.J.1005.2014.0346

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HEREDITAS ›› 2014, Vol. 36 ›› Issue (4): 346-353.doi: 10.3724/SP.J.1005.2014.0346

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Roles of hMMS2 gene in reversing the oxaliplatin tolerance of hu-man colon carcinoma cells

Lei Zhang¹, Yu Sui², Ting Wang³, Lijian Li¹, Yuanjie Li⁴, Caixia Jin², Fang Xu¹

1. Ningxia Key Laboratory of Reproduction and Genetics, College of Inspection, Ningxia Medical University, Yinchuan 750004, China;
2. Center for Translational Medicine, School of Medicine, Tongji University, Shanghai 200072, China

Received:2013-10-12 Revised:2014-01-29 Online:2014-04-20 Published:2014-03-20

Abstract

Abstract:

In this study, the roles of hMMS2 (human methyl methanesulfonate sensitive mutant 2) gene encoding the human ubiquitin-conjugating enzyme E2 variant 2 in the drug resistance in human colon carcinoma were investigated by using a well-differentiated human colorectal carcinoma L-OHP-resistant cell line, THC8307/L-OHP. THC8307/L-OHP cells were transfected via liposome along with plasmid pcDNA6.2-GW/EmGFP-miR-MMS2 expressing both miRNA against hMMS2 and GFP, followed by real-time fluorescent quantitative PCR and immunofluorescence to select stable transfectants with significantly reduced hMMS2 expression. Compared with untransfected or pcDNA6.2-GW/EmGFP vector-transfected cells, the hMMS2-depleted cells displayed significantly (P<0.05) reduced half inhibition concentration(IC50) resistance index (RI) and colony-forming efficiency (CFE) upon treatment with oxaliplatin (L-OHP), while its relative reverse efficiency(RRE) was significantly higher (P<0.05) than the control cells, indicating compromised ability of cell proliferation. Indeed, Rho-damine 123 staining and flow cytometry analyses revealed an increased rate of apoptosis in hMMS2-depleted cells while no difference in cell proliferation or apoptosis was observed between the two control cell lines. The above observations collec-tively indicate that suppression of hMMS2 reverses L-OHP tolerance in differentiated human colorectal carcinoma cells by promoting apoptosis.

Key words: RNA interference, platinum resistance, hMMS2, human well-differentiated colorectal carcinoma L-OHP-resistant cell line, apoptosis

Lei Zhang, Yu Sui, Ting Wang, Lijian Li, Yuanjie Li, Caixia Jin, Fang Xu. Roles of hMMS2 gene in reversing the oxaliplatin tolerance of hu-man colon carcinoma cells[J]. HEREDITAS, 2014, 36(4): 346-353.

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Roles of hMMS2 gene in reversing the oxaliplatin tolerance of hu-man colon carcinoma cells

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