Huqi San inhibits prehepatocarcinoma in rats probably through activating Hedgehog signaling pathway / 中国病理生理杂志

ABSTRACT

AIM: To explore the influence of Huqi San on the Hedgehog signaling pathway in rats with prehe-patocarcinoma.METHODS: The model of prehepatocarcinoma in the rats was established by a modified solt-farber method.The rats were intragastric administrated with Huqi San solution for 3 d after subtotal hepatectomy.Four weeks after administration of the Huqi San solution, the hepatic damage was observed by histopathological analysis.The protein expression of glutathione S-transferase-π (GST-π), alpha-fetoprotein (AFP), OV6, albumin (ALB) and glioma-associated oncogene homolog 2 (Gli2) was detected by immunohistochemistry and immunofluorescence staining.The expression of Sonic hedgehog (Shh), Smoothened (Smo), Gli2, cyclin D and cyclin E at mRNA and protein levels in the rats was determined by RT-qPCR and Western blot, respectively.The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were assayed using diagnostic kits.RESULTS: Compared with model group, Huqi San decreased the serum levels of ALT, AST and GGT, and alleviated the pathological changes in prehepatocarcinoma rats.Huqi San inhibited the protein expression of GST-π and AFP (P<0.05) in the prehepatocarcinoma rats.Huqi San also promoted the protein expression of OV6 and ALB (P<0.05).Furthermore, Huqi San activated Hedgehog signaling pathway and its downstream targeting molecules such as Shh, Smo, Gli2, cyclin D and cyclin E.In addition, the results in vitro showed that Huqi San may activate Hedgehog signaling pathway and promoted oval cell proliferation.CONCLUSION: Huqi San not only promotes hepatic progenitor cell proliferation, but also induces hepatic progenitor cell differentiation and inhibits prehepatocarcinoma in the rats probably via activating Hedgehog signaling pathway.