期刊
ONCOTARGET
卷 8, 期 16, 页码 26871-26885出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15845
关键词
oncolytic adenoviruses; AdC7; chimpanzee adenoviruses; p53-independent mitochondrial apoptosis; tumor treatment
资金
- National Natural Science Foundation of China [31670946]
- Knowledge Innovation Program from Chinese Academy of Sciences
- 100 Talent Program from Chinese Academy of Sciences
- Natural Science Foundation of Shanghai [17ZR1433500]
Among the oncolytic virotherapy, an emerging treatment for tumor, adenoviruses are widely used at present in preclinical and clinical trials. Traditionally, oncolytic adenoviruses were developed based on the human adenovirus serotype 5 (AdHu5). However, AdHu5 has the drawbacks of preexisting anti-AdHu5 immunity in most populations, and extensive sequestration of Adhu5 by the liver through hexon, blood coagulation factor X (FX), and FX receptor interactions. To tackle these problems, we explored a novel oncolytic adenovirus AdC7-SP/E1A-Delta E3 for cancer treatment. AdC7-SP/E1A-Delta E3 was constructed by replacing the E1A promoter with tumor specific promoter survivin promoter and deleting E3 region using direct cloning methods based on simian adenovirus serotype 24 (namely AdC7). We showed that AdC7-SP/ E1A-Delta E3 significantly killed tumor cell lines NCI-H508 and Huh7, and inhibited tumor growth in both NCI-H508 and Huh7 xenograft tumor models. Importantly, AdC7-SP/ E1A-Delta E3 exhibited the antitumor efficacy via systemic administration. Mechanistically, infected cells were killed by AdC7-SP/E1A-Delta E3 via the p53-independent mitochondrial apoptosis pathway in which phosphorylation of BAD markedly declined and the expresses of Bik significantly went up. Therefore, AdC7-SP/E1A-Delta E3 is a promising candidate for liver and colon tumor treatment.
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