Efficacy of an Oncolytic Adenovirus Driven by a Chimeric Promoter and Armed with Decorin against Renal Cell Carcinoma

Abstract

Virus-targeted therapy for tumors can effectively prolong the survival rate of patients and has become a new trend for cancer biotherapy. Oncolytic adenovirus (OAd) can specifically replicate in tumor cells, allowing the therapeutic genes carried to be rapidly copied. As known, solid tumors are always hypoxic, and researchers often overlook a key point, the replication of OAd depends not only on its own activity but also on the cellular hypoxic environment in which the virus replicates. In this study, we constructed an OAd carrying Decorin, HRE-Ki67-Decorin, combining the Ki67 promoter upstreamed with hypoxia-response element (HRE) sequences to drive adenoviral E1A. The OAd HRE-Ki67-Decorin had better replication ability under hypoxic conditions, downregulated cellular immunosuppressed growth factor TGF-β. In addition, HRE-Ki67-Decorin was potent in suppressing tumor growth and participated in the assembly of tumor extracellular matrix by expressing Decorin in subcutaneous renal cancer cell tumor models. Tumor sections from HRE-Ki67-Decorin-treated tissues had less collagen fibers and more spread of virus among tumor tissues. These results indicated that chimeric HRE-Ki67 promoter-regulated OAd carrying Decorin might be an effective anticancer treatment strategy.