Reversing multidrug resistance by RNA interference through the suppression of MDR1 gene in human hepatoma cells

doi:10.3748/wjg.v12.i21.3332

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Liver Cancer

World J Gastroenterol. Jun 7, 2006; 12(21): 3332-3337
Published online Jun 7, 2006. doi: 10.3748/wjg.v12.i21.3332

Reversing multidrug resistance by RNA interference through the suppression of MDR1 gene in human hepatoma cells

Xiao-Ping Chen, Qi Wang, Jian Guan, Zhi-Yong Huang, Wan-Guang Zhang, Bi-Xiang Zhang

Xiao-Ping Chen, Qi Wang, Jian Guan, Zhi-Yong Huang, Wan-Guang Zhang, Bi-Xiang Zhang, Department of Surgery and Hepatic Surgery Center, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China

Supported by the National Natural Science Foundation of China, No. 30400431

Correspondence to: Xiao-Ping Chen, M D, Professor, Chairman, Department of Surgery and Hepatic Surgery Center, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. chenxp@medmail.com.cn

Telephone: +86-27-83662599 Fax: +86-27-83662851

Received: November 10, 2005
Revised: November 28, 2005
Accepted: December 22, 2005
Published online: June 7, 2006

Abstract

AIM: To reverse the multidrug resistance (MDR) by RNA interference (RNAi)-mediated MDR1 suppression in hepatoma cells.

METHODS: For reversing MDR by RNAi technology, two different short hairpin RNAs (shRNAs) were designed and constructed into pGenSil-1 plasmid, respectively. They were then transfected into a highly adriamycin-resistant HepG2 hepatoma cell line (HepG2/ADM). The RNAi effect on MDR was evaluated by real-time PCR, cell cytotoxicity assay and rhodamine 123 (Rh123) efflux assy.

RESULTS: The stably-transfected clones showed various degrees of reversal of MDR phenotype. Surprisingly, the MDR phenotype was completely reversed in two transfected clones.

CONCLUSION: MDR can be reversed by the shRNA-mediated MDRI suppression in HepG2/ADM cells, which provides a valuable clue to make multidrug-resistant hepatoma cells sensitive to anti-cancer drugs.

Keywords: Multidrug resistance; ShRNA; MDR1; Hepatocellular carcinoma