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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 oncolytic adenovirus depends not only on its own activity but also on the cellular hypoxic environment in which the virus replicates. Here we constructed an oncolytic adenovirus carrying Decorin, HRE-Ki67-Decorin, combining the Ki67 promoter up-streamed with hypoxia response element (HRE) sequences to drive adenoviral E1A. The oncolytic adenovirus HRE-Ki67-Decorin had better replication ability under hypoxic conditions, down-regulated 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 (ECM) by expressing Decorin in subcutaneous renal cancer cells 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 anti-cancer treatment strategy.
PMID: 32216478 [PubMed - as supplied by publisher]