Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis.
OBJECTIVE
To study the inhibitory effect of Huqi San (Qi-protecting powder) on rat prehepatocarcinoma induced by diethylinitrosamine (DEN) by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes.


METHODS
A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene (AAF) to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. gamma-glutamy-transpeptidase-isoenzyme (gamma-GTase) was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine (OHdG) formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods.


RESULTS
The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before (1 wk) and after DEN exposure (4 wk). Huqi San-treated rats showed a significant decrease in number of gamma-GT positive foci (P < 0.001, prevention group: 4.96 +/- 0.72 vs 29.46 +/- 2.17; large dose therapeutic group: 7.53 +/- 0.88 vs 29.46 +/- 2.17). On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats.


CONCLUSIONS
Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer. Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesions induced by DEN.
Li
Xia
X
Pathophysiological Department, Capital Medical University, Beijing 100069, China.
Shi
Zheng-Ming
ZM
Feng
Ping
P
Wen
Zhao-Yang
ZY
Wang
Xue-Jiang
XJ
D000477:Alkylating Agents; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D019413:Qi; D051381:Rats
D000477:Alkylating Agents; D004365:Drugs, Chinese Herbal; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D004052:Diethylnitrosamine
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