期刊
HUMAN GENE THERAPY
卷 20, 期 8, 页码 818-830出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2008.205
关键词
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资金
- Zhejiang Science and Technology [2007C33027]
- National Nature Science Foundation of China [30623003, 30800093]
- National Basic Research Program of China [2004 CB51804]
- Chinese Academy of Science [KSCX2-YW-R-09, R-04]
- Zhejiang Sci-Tech University [0616033]
Interleukin (IL)-24 is an excellent therapeutic gene for cancer therapy. In this work, IL-24 was inserted into Ad.sp-E1A((Delta 24)), an oncolytic adenovirus with a 24-bp deletion in the E1A gene, which was driven by the survivin promoter to form Ad.sp-E1A((Delta 24))-IL-24. Ad.sp-E1A((Delta 24))-IL-24 has an excellent antitumor effect in vitro for human nasopharyngeal, liver, lung, and cervical carcinoma cell lines but does no or little damage to normal cell lines L-02 and WI38. Furthermore, it achieved nearly complete inhibition (although not elimination) of NCI-H460 lung carcinoma growth in nude mice. The antitumor efficacy of Ad.sp-E1A((Delta 24))-IL-24 on NCI-H460 cells was clearly mediated by apoptosis, because it induced caspase-3 and poly(ADP-ribose) polymerase cleavage. This is the first report of Ad.sp-E1A((Delta 24))-IL-24 with such an excellent, broad, and specific antitumor effect in vitro and nearly complete inhibition of lung tumor growth in vivo.
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