Hedgehog signaling pathway activation in hepatocellular carcinoma / 中华普通外科杂志

ABSTRACT

Objective To investigate the expressions of Hedgehog sisnaling pathway genes in hepatocellular carcinoma tissues(HCC),and the effect of specific Hedgehog pathway inhibitor(KAADcyclopamine)on the growth of HCC cells and the expressions of Hedgehog genes. Methods The expression of Hedgehog signaling pathway components(Ihh,Ptch,Smo and Gli)was investigated in 14 HCC tissue slices,4 HCC cell lines and a normal hepatic cell line by using immunochemistry.The expression of Ihh,Ptch,Smo and Gli proteins was investigated in 9 HCC tissue specimens and 6 normal hepatic tissue specimens by using Western blotting.The expression of Ihh、Ptch、Smo、Gli and Hip genes was investigated by RT-PCR.Results The positive ratio of Gli,Ptch,Ihh and Smo were 42.9%,71.4%,71.4% and 85.7% in 14 HCC tissue slices,respectively.The expressions of Gli protein and Gii gene were up regulated while the expression of Hip gene was down regulated in HCC specimens compared with normal hepatic tissue specimens.Hedgehog signaling pathways in HCC cell lines HepG2,Bel-7402 and QGY-7701 were activated;KAAD-cyclopamine,a specific inhibitor of the Hedgehog signaling pathway,down regulated cell growth and the expressions of Ptch and Gli genes in the 3 HCC cell lines(Ptch genetHepG2=3.78,tBel-7402=9.03,tQGY-7701=5.63;Gli genetHepG2=9.61,tBel-7402=4.15,tQGY-7701=20.30,P＜0.05 in each group).The expression of Hip gene was up regulated in QGY-7701 after treated with KAAD-cyclopamine(t=4.70,P＜0.05).Conclusion The expression of main Hedgehog signaling pathway components were detected in HCC,KAAD-cyclopamine specifically inhibited the Hedgehog signaling pathway.