BMP-2在肝癌增殖侵袭中的血管生成作用及其相关分子机制研究

骨形态发生蛋白2（BMP-2）在肝癌的增殖侵袭中起重要作用。我们前期研究表明BMP-2可促进肝癌的增殖和侵袭，通过MAPK/ERK信号通路上调MMP-2、MMP-9和下调E-cad的表达及通过MAPK/P38信号通路上调VEGF-C是其可能的分子机制。由于MMP、E-cad、VEGF-C均为重要的肿瘤血管生成因子，我们推测BMP-2促进肝癌增殖侵袭可能与血管生成有关。本课题拟采用慢病毒介导的基因超表达和RNA干扰检测BMP-2对血管生成的影响、免疫共沉淀检测BMP-2-血管生成因子共表达对肝癌增殖侵袭的影响、激光共聚焦观察BMP-2对肝癌微血管生成能力的影响等方法，通过体内外实验探讨BMP-2在肝癌增殖侵袭中血管生成的作用及其多信号通路调节机制。本研究从血管生成这个新视点来进一步探讨BMP-2对肝癌增殖侵袭的作用，有望从深层次揭示肝癌增殖侵袭的分子机制，为肝癌临床治疗探寻到新的治疗靶点。

The bone morphogenetic protein 2 (BMP-2) plays an important role in the proliferation and invasion of liver cancer. Our previous studies have shown that BMP-2 can promote the proliferation and invasion of liver cancer. The molecular mechanism may be caused by the up-regulated expression of MMP-7, MMP-9 and the down-regulated expression level of E-cadherin through MAPK/ERK signal pathway, and the up-regulated expression of VEGF-C through MAPK/P38 signal pathway is also probably one of the mechanisms. Because MMP, E-cad, VEGF-C are important tumor angiogenesis factors, we presume that BMP-2 promote HCC's proliferation and invasion related angiogenesis. This study intends to use gene overexpression and lentivirus-mediated RNA interference detection of BMP-2 on angiogenesis effects, co-immunoprecipitation to detect BMP-2-angiogenic factor for HCC proliferation and invasion of coexpression and the Laser Scanning Confocal Microscopy observation BMP -2 impact on the ability of HCC angiogenesis to investigate multiple signaling pathways regulating mechanisms of BMP-2 in HCC proliferation and invasion in angiogenesis by in vivo and in vitro experiments. This study further detects the effect of BMP-2 in HCC's invasion and proliferation, from this new viewpoints of angiogenesis, and deep-seated reveals the molecular mechanisms of HCC's invasion and proliferation for the clinical treatment of liver cancer to explore new therapeutic targets.