E2F promoter-regulated oncolytic adenovirus with p16 gene induces cell apoptosis and exerts antitumor effect on gastric cancer.
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.
Ma
Juming
J
Department of Internal Medicine, 117 Hospital of Chinese People's Liberation Army, Hangzhou, People's Republic of China.
Ma
J
J
He
Xiaoping
X
He
X
X
Wang
Weiguo
W
Wang
W
W
Huang
Yao
Y
Huang
Y
Y
Chen
Lin
L
Chen
L
L
Cong
Wenming
W
Cong
W
W
Gu
Jianzhong
J
Gu
J
J
Hu
Huizhen
H
Hu
H
H
Shi
Jianguo
J
Shi
J
J
Li
Linfang
L
Li
L
L
Su
Changqing
C
Su
C
C
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
D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008156:Luciferases