E2F Promoter-Regulated Oncolytic Adenovirus with p16 Gene Induces Cell Apoptosis and Exerts Antitumor Effect on Gastric Cancer
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Replication-competent adenovirus (RCAd) constitutes an alternative in cancer therapy. For obtaining advanced RCAd generations with high oncolytic capability and a good safety profile, we constructed an E2F promoter-regulated RCAd carrying p16 gene, AdE2F-p16, in which the E1a gene was controlled by the E2F promoter. The experimental data showed that the E2F promoter endowed AdE2F-p16 with high specificity in cancer cells. While rarely replicating in normal cells, AdE2F-p16 could replicate in p16-deficient cancer cells, with 2,937- to 160,000-fold increased replicative capability in different cancer cell lines. AdE2F-p16 expressed p16 within cancer cells and led to potent antitumor efficacy in gastric cancer xenografts in nude mice, with a tumor inhibition rate of 59.14%. Due to the combined effects of cancer cell apoptosis induced by p16 expression and oncolysis by virus replication, the E2F promoter-regulated, p16-armed RCAd provides a promising strategy for cancer gene therapy.
KeywordsReplication-competent adenovirus Gene therapy p16 gene E2F promoter Gastric cancer Apoptosis
This work was supported by grants from the National Natural Scientific Foundation of China (No. 30572149) and the Scientific and Technological Project of Zhejiang Province, China (No. 2006C30021).
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