Treatment of chronic proliferative cholangitis with c-myc shRNA.
OBJECTIVE
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 beta-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 beta-glucuronidase. Further investigation indicated that c-myc shRNA-3 had a better inhibitory effect on CPC.


CONCLUSIONS
Treatment with c-myc shRNA-3 can control CPC and reduce the lithogenic potentiality of CPC.
Li
Fu-Yu
FY
Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Sichuan Province, China. lfy_74@vip.163.com
Cheng
Nan-Sheng
NS
Cheng
Jing-Qiu
JQ
Mao
Hui
H
Jiang
Li-Sheng
LS
Li
Ning
N
He
Sheng
S
D000818:Animals; D002761:Cholangitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D042882:Gallstones / Q000517:prevention & control; D016259:Genes, myc; D005966:Glucuronidase / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence
D024061:Collagen Type III; D055271:Mucin 5AC; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D005966:Glucuronidase; D006909:Hydroxyproline