p53是研究最为广泛的抑癌基因之一，相应治疗药物已应用于临床，但疗效普遍不佳。这是由于肿瘤中存在p53突变，mutp53不但丧失原有抑癌功能，且能促进肿瘤生长并拮抗wtp53的肿瘤治疗作用。ARF是一种重要的肿瘤抑制因子，它的失活常导致肿瘤的发生。我们的研究表明，ARF对mutp53肝癌细胞的抑癌作用明显大于wtp53型，且能在mutp53肝癌细胞中上调p53下游靶分子p21及p53抑制因子MDM2。提示ARF对mutp53肝癌细胞存在异常调节机制，我们推测是由于ARF对mutp53的构象矫正，从而反转mutp53的功能，使其恢复p53的肿瘤抑制功能。本研究拟(1)检测不同肝癌细胞系中p53突变位点和方式；(2)体内外实验检测ARF对不同p53表型肝癌细胞的抑制作用；(3)检测ARF对特异性mutp53是否具有构象矫正作用。本研究的完成将为探索p53肿瘤治疗新方法奠定基础和提供实验依据。

P53 is one of the most widely studied tumor suppressor genes that its curative has been used in clinic. However, the curative's effect is generally poor due to p53 gene mutations in tumor . The mutant p53 gene not only loses original tumor suppressor function ,but also can promote tumor growth and antagonize tumor therapy of wild-type p53 s'.ARF is an important tumor suppressor that its inactivation can result in tumorigenesis. Our study shows that the ARF's tumor suppressor role in liver cancer cells that of mutant p53 was significantly greater than that of wild-type p53, and it can also up-regulate p21which is the downstream target molecules of p53 and MDM2 which is p53's inhibitor .That all above firstly prompted there is an abnormal regulatory mechanism of ARF in liver cancer cells. our assumption is that ARF may correct the conformation of mutant p53 gene so that it reverses the feature of mutant p53 to restore the tumor suppressor function of p53. In this study,(1)Detecting where and how the p53 mutations take place in different liver cancer cell lines;(2)Through experiment to detect the tumor inhibition of ARF in differently p53 phenotypes HCC in vitro and vivo;(3)To detect whether ARF has the function of conformation correction in specific p53 phenotype HCC.The completion of this study will lay the foundation and provide experimental basis for further researches in new methods of tumor therapy.