Adenovirus-mediated decorin expression induces cancer cell death through activation of p53 and mitochondrial apoptosis

Abstract

Decorin (DCN) is a small leucine-rich proteoglycan that plays an important role in the regulation of apoptosis, proliferation, intercellular contact, and cell migration. Here we have investigated the detailed mechanism of apoptotic cell death induced by DCN expression. A marked increase in cytotoxicity was observed for both DCN-expressing replication-incompetent (dE1/DCN) and -competent (dB/DCN) adenoviruses (Ads) compared to the corresponding control Ads. FACS and TUNEL assays revealed that the expression of DCN induced apoptotic cell death. Specifically, the expression and stability of p53 were increased by DCN. In addition, western blot data showed that DCN expression activated mitochondrial apoptosis by increasing the expression level of p53. Similarly, DCN-expressing oncolytic Ads induced a greater antitumor effect in a murine xenograft model compared with control Ads. Tissue staining and western blot data from in vivo experiments demonstrated significantly higher levels of apoptosis in tumor tissues from mice treated with DCN-expressing Ads compared to those treated with control Ads. Collectively, these data support that cell killing effect is enhanced with Ad-mediated DCN expression via the induction of p53-mediated mitochondrial apoptosis, which could be a valuable benefit for antitumor efficacy.