整合素avβ3介导了细胞和细胞外基质、细胞和细胞之间的相互黏附，在肿瘤血管生成的过程中发挥着重要作用；经动脉化疗栓塞术(TACE)是中晚期肝癌主要的治疗方式，但容易导致VEGF升高，促进肿瘤血管生长。申请人前期发现索拉非尼能有效对抗TACE术后大肝癌血管的生成，同时证实avβ3通过OPN和Pim-1调节肿瘤血管重建。然而，索拉非尼联合TACE治疗肝癌中对整合素avβ3的作用机制尚未阐明。鉴此，本研究拟：1. 通过体内外实验明确索拉非尼对肝癌血管内皮细胞avβ3表达的作用机制。2. 在体探讨TACE术后肝癌缺氧对avβ3的表达水平的影响。3.分析索拉非尼联合TACE治疗肝癌中对整合素avβ3表达及其在VEGF、Notch、 OPN血管生成信号传导通路中的影响。本研究成果将揭示索拉非尼联合TACE治疗肝癌中通过整合素avβ3对血管生成的调控机制，为确立肝癌新的个体化联合治疗模式提供科学依据。

Integrin avβ3 plays an important role in modulating proangiogenic EC responses following VEGFR2 engagement by VEGF.TACE (Transcatheter Arterial Chemoembolization) is the main treatment in patients with advanced HCC. However, After TACE, the residual cancer cells are in an extensive hypoxic or even anoxic environment. Hypoxia can lead to adaptive responses by VEGF overexpression. In primarily study, we found that Sorafenib effectively inhibits the angiogenesis of large hepatocellular carcinoma, and also confirmed that avβ3 integrin regulates tumour blood vessel development and tumour cell proliferation by OPN and Pim-1.However, the role of avβ3 integrin in angiogenesis in the treatment of Sorafenib combined with TACE on HCC is still unclear. Thus, the present study plan aims to 1.To investigate the effect mechanism of Sorafenib on expression of Integrin αVβ3 of vascular endothelial cells of HCC in vitro and in vivo. 2. To explore the influence of hypxic enviroment on expression of avβ3 of HCC after TACE in vivo. 3. To analysis the effective mechanism of Sorafenib regulating VEGF, Notch, OPN signaling pathways by Integrin αvβ3 during TACE processing. The results of this research will reveal the effective mechanism of that Sorafenib regulates tumor angiogenesis by Integrinαvβ3 in the treatment of Sorafenib combined with TACE on HCC, These observations emphasize the evidence of new individualized combined treatment for HCC.