我国肝癌患病率约占全世界一半以上。对于失去外科手术机会或术后复发患者，肝动脉化疗栓塞(TACE)是其首选治疗方法，但五年生存率低于10%。原因在于TACE治疗仅栓塞现存肿瘤血管，无法抑制肿瘤血管新生。肿瘤血管新生是肝癌复发和转移的基础，如何抑制肿瘤血管新生是其研究的热点、难点问题。本课题将通过不同给药途径和不同剂量的动物实验组对比分析、利用影像学、组织学、细胞学等技术对雷帕霉素联合TACE治疗肝癌动物模型的实验价值及剂量-效应-毒性-免疫功能抑制关系进行评估；应用原位杂交、western blot、免疫组化和RT-PCR技术检测HIF-1a、VEGF、iNOS、JNK、IKK、BCL-xL和P53的基因、mRNA和蛋白表达水平，探索雷帕霉素抑制肝癌肿瘤血管新生及肿瘤增殖作用的机制。本课题将为中晚期、无手术机会和术后复发的肝癌患者探索新治疗方法的实施提供重要动物实验依据，提高肝癌的临床疗效。

It has been estimated that more than 50% of the world’s hepatocarcinoma cases occurred in China. Although transcatheter arterial chemoembolization (TACE) has been considered as one of the most important interventional therapies for patients with unresectable or recurrent hepatocarcinoma, the five-year survival rate in these patients after TACE is still below 10%. This may be due to the embolization effect of TACE being restricted on existing tumor blood vessels, while TACE has no effect on tumor angiogenesis. Tumor angiogenesis has been considered as the basis of recurrence and metastasis for hepatocarcinoma. Therefore, how to inhibit angiogenesis in hepatocarcinoma has become a hot and important topic in clinical research. This project will evaluate the efficacy of combination of arterial chemoembolization with rapamycin in treatment of animal model with hepatocarcinoma. Meanwhile, the does of the combination will be optimized according to the efficacy, toxicity and immune response, through comparision of different routes and doses of medicine administration. A series of techniques will be applied in this project, including imaging, histology, and cytology. To investigate the mechanisms of rapamycin in inhibiting tumor angiogenesis and tumor proliferation, in situ hybridization, Western blot, immunohistochemistry, and RT-PCR will be used to monitor the gene, mRNA and protein levels of HIF-1a、VEGF、iNOS、JNK、IKK、BCL-xL and P53. This project will be a valuable contribution to our understanding about the role of immunosuppression in the inhibition of tumor angiogenesis in unresectable or recurrent hepatocarcinoma and will provide TACE with rapamycin as a potential new therapeutic approach for improving hepatocarcinoma treatment.