Adenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions

作者：Jiang, Yunbo; Chen, Huihua; Jia, Haiquan; Xu, Yuanji; Liu, Gang; Wang, Yan; Yang, Xiaohe; Lu, Yinglin^*

来源：Experimental and Therapeutic Medicine, 2010, 1(2): 363-368.

DOI：10.3892/etm_00000057

• p53AIP1
• p53
• MDM2
• cell cycle
• apoptosis
• gene therapy

We generated replication-defective adenovirus Ad-p53AIPI and studied its anti-tumor efficacy both in vitro and in vivo. We demonstrated that Ad-p53AIP1 infection elicited high levels of p53AIP1 expression in cancer cells. We also found that Ad-p53AIPI expression induced marked apoptosis and cell cycle arrest in HepG2 cells. Moreover, Ad-p53AIP1 infection significantly inhibited the tumorigenesis of 4T1 mouse mammary cancer cells in vivo. In particular, we discovered that p53AIP1 overexpression up-regulated the protein levels of p53 in HepG2 cells, which was accompanied by down-regulation of MDM2 mRNA and protein, suggesting an interaction between MDM2 and p53 in p53AIP1-induced apoptosis and cell cycle arrest. Our data demonstrated the feasibility of Ad-p53AIP1-mediated cancer gene therapy. p53A IPI-induced up-regulation of p53 protein through MDM2 suggests that p53AIP1 gene therapy may be more advantageous in tumors expressing high levels of oncoprotein MDM2 or having a mutation in MDM2 inhibitor p16INK4.

• 出版日期2010-3