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

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

doi:10.3892/etm_00000057

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

Authors:
- Yunbo Jiang
- Huihua Chen
- Haiquan Jia
- Yuanji Xu
- Gang Liu
- Yan Wang
- Xiaohe Yang
- Yinglin Lu
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Affiliations: Department of Pathobiology, Institute of Basic Medical Sciences, Beijing 100850, P.R. China
Published online on: March 1, 2010 https://doi.org/10.3892/etm_00000057
Pages: 363-368

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Abstract

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.

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