Abstract 595: Single adenovirus-mediated simultaneous expression of p53 and the artificial microRNAs targeting anti-apoptotic p53 target genes

Abstract

Abstract Gene transfer involving p53 is viewed as a potentially effective cancer therapy, but does not result in a good therapeutic response in all human cancers. Several p53 target genes have an inhibitory effect on p53-mediated apoptosis. Therefore, if the induction of these genes by p53 is selectively suppressed, the therapeutic effectiveness would be improved. In previous study, we constructed a replication-deficient recombinant adenovirus that encoded co-cistronic p53 and artificial microRNAs (miRNAs) targeting p21, a representative p53 target gene which have an anti-apoptotic effect, resulting in p53 expression and the suppression of p21 induction simultaneously. In colorectal and hepatocellular carcinoma cells, infection with the adenovirus vector augmented apoptosis and suppressed tumor growth as compared to an adenovirus that expressed p53 alone in vitro and in vivo. In this study, we additionally inserted miRNA sequences targeting other anti-apoptotic genes such as MDM2 to the vector and evaluated the therapeutic effectiveness of p53 expression in combination with the suppression of several anti-apoptotic p53 target genes. Infection with the vector suppressed the induction of anti-apoptotic target genes and induced apoptosis more efficiently in cancer cells. These results suggest that adenovirus-mediated transduction of p53 and miRNAs targeting anti-apoptotic p53 target genes is useful for therapy of human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 595.