title: E2F promoter-regulated oncolytic adenovirus with p16 gene induces cell apoptosis and exerts antitumor effect on gastric cancer.
abstract: 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.
authors.affiliation: Department of Internal Medicine, 117 Hospital of Chinese People's Liberation Army, Hangzhou, People's Republic of China.
authors.forename: Juming
authors.initials: J
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: Xiaoping
authors.initials: X
authors.lastname: He
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: Weiguo
authors.initials: W
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Wenming
authors.initials: W
authors.lastname: Cong
authors.forename: W
authors.initials: W
authors.lastname: Cong
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: Huizhen
authors.initials: H
authors.lastname: Hu
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shi
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.forename: Linfang
authors.initials: L
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
authors.forename: C
authors.initials: C
authors.lastname: Su
mesh_terms: D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D019942:Genes, p16 / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D050130:Oncolytic Virotherapy / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000821:virology; D014779:Virus Replication / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008156:Luciferases