肝细胞肝癌治疗是重大课题。前期结果：复方芪参提取物（CASE）通过干预TGF-β/Smad信号通路尤其是Samd3的C末端和连接区磷酸化（pSmad3C/3L）发挥抗肝癌作用；预实验结果：CASE促进大鼠肝癌模型中miR145表达上调和miR21表达下调。推测,TGF-β/Smad通路与miR-145/miR-21间的交互作用可能是CASE抗肝癌的重要机制。故拟在HepG2细胞、肝癌荷瘤裸鼠模型中，用Smad3C/3L磷酸化位点突变质粒及agomir/antagomir干预pSmad3C/3L及miRNA表达，采用WB、qRT-PCR、荧光素酶报告基因实验等方法检测通路中成员蛋白、miRNA的表达及其相互影响，观察TGF-β/Smad信号通路尤其是pSmad3C/3L与miR-145、miR-21的交互作用及CASE对该作用的干预，阐明CASE抗肝癌分子机制，为其临床防治肝癌提供理论依据。

Hepatocellular carcinoma (HCC) therapy is a difficult problem for human. Our previous results showed that Compound Astragalus and Salvia miltiorrhiza extract (CASE) could exert anti-HCC effect by interfering with TGF-β/Smad signaling pathway, especially regulating the phosphorylation of Smad3 at the C-terminal or linker region (pSmad3C、pSmad3L). In addtion, our preliminary experiment showed that CASE could increase miR-145 expression, while decrease miR-21 expression, in rats induced by diethylinitrosamine. We presume that the interplay between miR-145、miR-21 and TGF-β/Smad signaling pathway might be the important mechanisms of CASE's anti-HCC action. Therefore, we propose to investigate the interaction between miRNA and TGF-βsignaling pathway under the influence of CASE in HepG2 cells in vitro and subcutaneous hepatoma xenografts of BALB/c nude mice in vivo by using agomir、antagomir or the mutanted plasmids in which the kinase sites at the C-terminal or linker region of Smad3. The expressing level of the protein、gene in the signaling pathway、microRNA will be detected by using western blot、qRT-PCR and luciferase assay. This study attemps to elucidate the molecular mechanisms of CASE's anti-HCC effect. The results may provide a theoretical foundation for clinical application of CASE in HCC treatment.