Open AccessAdenovirus Ad-p53AIP1-mediated gene therapy and its regulation of p53-MDM2 interactions
Author(s) -
Yunbo Jiang,
Huihua Chen,
Haiquan Jia,
Yujin Xu,
Gang Liu,
Yan Wang,
Xiaohe Yang,
Yinhui Lu
Publication year - 2010
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm_00000057
Subject(s) - mdm2 , carcinogenesis , biology , oncogene , cell cycle , apoptosis , cancer research , genetic enhancement , cancer , in vivo , tumor suppressor gene , adenoviridae , cancer cell , gene , genetics
We generated replication-defective adenovirus Ad-p53AIP1 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-p53AIP1 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. p53AIP1-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.