Smo、Gli1在大鼠肝癌中的表达及维生素D3对Smo、Gli1的抑制

摘要

背景与目的:研究表明Sonic Hedgehog(Shh)信号通路与肿瘤的发生有重要联系,本实验通过检测大鼠肝癌模型中Smo、Gli1的表达,探讨其与肝癌发生发展的关系,了解维生素D3(Vitamin D3,VitD3)对Smo、Gli1的作用.方法:取48只5～6周龄的健康雄性SD大鼠,并随机分组.对照组:一般饲养的8只大鼠;DEN组:二乙基亚硝胺(diethylnirtosamine,DEN)诱癌的20只大鼠;DEN+VitD3组:DEN+VitD3干预的20只大鼠;分别于实验12周和20周处死各组一半数量的大鼠,采用Western blot检测大鼠肝脏中Smo、Gli1蛋白的表达,实时荧光定量PCR检测两种蛋白mRNA的表达.结果:对照组中12周和20周大鼠肝脏的Smo、Gli1的mRNA及蛋白的表达差异无统计学意义(P＞0.05);DEN组或DEN+VitD3组中20周的Smo、Gli1表达高于12周(P＜0.05);相同实验周期:DEN的Smo、Gli1表达高于VitD3组(P＜0.05);与其他两组相比,对照组表达最低(P＜0.01).结论:Smo、Gli1可能参与肝癌的发生发展,VitD3对Smo、Gli1具有一定抑制作用.%Background and purpose: It has been reported that Sonic Hedgehog (SHH) signaling pathways are involved in the progress of carcinoma.This experiment is designed to detect the expressions of Smo and Gli1 in induced primary hepatocellular carcinomas modes, study the relationship between Smo, Gli1 and the progress of HCC, and explore the effects of VitD3 on the Shh signaling pathway.Methods: For 5 to 6 weeks, a totally of 48 old but healthy male SD rats were randomized into 3 groups.These groups were respectively implanted with nothing (control group), DEN (DEN group), and DEN+VitD3 (DEN+VitD3 group).The specimens were harvested separately at the end of 12 and 20 weeks.The expressions of Smo and Gli1 were detected using Western blot and Real time PCR.Results: In the control group, the expressions of Smo and Gli1 were not significantly different by the end of 12 and 20 weeks (P＞0.05).In the DEN group or DEN+VitD3 group, the expressions at the end of 12 weeks were higher than those at the end of 20 weeks (P＜0.05).At the end of 12 or 20 weeks, the expressions of Smo and Gli1 in the DEN group were elevated in comparison to the DEN+VitD3 group (P＜0.05).The expressions in the control group were relatively the lowest (P＜0.01).Conclusion: Smo and Gli1 might participate in the progress of HCC.Vitamin D3 may be an inhibitor of Smo and Gli1 in the SHH signaling pathway.