Original Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Jan 7, 2009; 15(1): 95-101
Published online Jan 7, 2009. doi: 10.3748/wjg.15.95
Treatment of chronic proliferative cholangitis with c-myc shRNA
Fu-Yu Li, Nan-Sheng Cheng, Jing-Qiu Cheng, Hui Mao, Li-Sheng Jiang, Ning Li, Sheng He
Fu-Yu Li, Nan-Sheng Cheng, Li-Sheng Jiang, Ning Li, Sheng He, Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Jing-Qiu Cheng, Hui Mao, Key Laboratory of Transplantation Engineering and Immunology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Li FY and He S designed the research; Cheng NS and Jiang LS established the animal model and immunohistochemistry; Li N performed the histochemistry and biochemistry; Cheng JQ and Mao H performed the real-time PCR and Western blot.
Correspondence to: Fu-Yu Li, Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China. lfy_74@vip.163.com
Telephone: +86-28-85422465
Fax: +86-28-85164029
Received: April 19, 2008
Revised: July 14, 2008
Accepted: July 21, 2008
Published online: January 7, 2009
Abstract

AIM: To investigate the feasibility and effectiveness of c-myc shRNA in inhibiting the hyperplastic behavior and lithogenic potentiality of chronic proliferative cholangitis (CPC), in order to prevent stone recurrence and biliary restenosis.

METHODS: An animal model of CPC was established by giving intralumenally 0.5 mL of c-myc shRNA. Then, the effects of c-myc shRNA on hyperplastic behavior and lithogenic potentiality of CPC were evaluated by histological observation, immunohistochemistry, real-time PCR and Western blotting for c-myc, proliferating cell nuclear antigen (PCNA), procollagen III, mucin 5AC, enzymatic histochemistry for β-glucuronidase, and biochemistry for hydroxyproline in the diseased bile duct.

RESULTS: Treatment with c-myc shRNA efficiently suppressed the hyperplasia of biliary epithelium, submucosal gland, and collagen fiber by inhibiting mRNA and protein expression of c-myc. More importantly, it decreased the lithogenic potentiality of CPC by inhibiting the expression of mucin 5AC and the secretion of endogenous β-glucuronidase. Further investigation indicated that c-myc shRNA-3 had a better inhibitory effect on CPC.

CONCLUSION: Treatment with c-myc shRNA-3 can control CPC and reduce the lithogenic potentiality of CPC.

Keywords: chronic proliferative cholangitis, Hepatolithiasis, Recurrence, C-myc, Prevention