Practical value of applying cdc2 kinase shRNA to chronic proliferative cholangitis in treatment of hepatolithiasis.
OBJECTIVE
High stone recurrence and biliary restenosis rates in hepatolithiasis patients have been confirmed to be closely related to postoperatively-remnant chronic proliferative cholangitis (CPC), but effective management strategies have not yet been developed. Since CPC is a type of hyperplastic disease, this study was designed to investigate inhibitory effectiveness of cdc2 k ShRNA on hyperplastic behavior and lithogenic potentiality of CPC.


METHODS
0.5 ml of P-cdc2 shRNA was injected transpapillarily into the bile duct lumen in a rat model of cholangitis. Then, the effects of cdc2 k ShRNA on CPC were evaluated by histology, immunohistochemistry, RT-PCR, Western blot, biochemistry and enzymatic histochemistry for cdc2 k, PCNA, Ki-67, Procollagen III, Mucin 5AC, beta-glucuronidase and hydroxyproline.


RESULTS
cdc2 k shRNA-3 treatment could efficiently inhibit hyperplasia of biliary epithelium, submucosal gland, and collagen fiber by inhibiting mRNA and protein expressions of the proliferation-related gene, cdc2 k, PCNA and Ki-67, thus holding the promise to control or reverse CPC and its secondary biliary stricture. Also of note, this novel treatment may decrease the lithogenic potential of CPC via inhibition of endogenous beta-glucuronidase and Mucin 5AC expression, hereby facilitating the prevention of stone recurrence.


CONCLUSIONS
cdc2 k shRNA-3 treatment could effectively inhibit the hyperplastic behavior and lithogenic potentiality of CPC, which might help to prevent the biliary restenosis and stone recurrence.
Li
Fu-Yu
FY
Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu, China.
Cheng
Nan-Sheng
NS
Cheng
Jing-Qiu
JQ
Mao
Hui
H
Jiang
Li-Sheng
LS
Li
Quan-Sheng
QS
Zhou
Yong
Y
D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics; D002761:Cholangitis / Q000473:pathology / Q000628:therapy*; D002908:Chronic Disease; D005966:Glucuronidase / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D020347:Lithiasis / Q000473:pathology / Q000628:therapy*; D008107:Liver Diseases / Q000473:pathology / Q000628:therapy*; D008297:Male; D055271:Mucin 5AC / Q000032:analysis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019394:Ki-67 Antigen; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D016203:CDC2 Protein Kinase; D005966:Glucuronidase; D006909:Hydroxyproline