Potent Antitumor Effect of Interleukin-24 Gene in the Survivin Promoter and Retinoblastoma Double-Regulated Oncolytic Adenovirus
| Autor: | Rui Cheng Wei, Yu Mei Wu, Xue Tian Yue, Xinyuan Liu, Kang Jian Zhang, Gongchu Li, Su Yang Zhong, Xin Cao, Yigang Wang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Oncolytic adenovirus
Cell Survival Survivin Genetic enhancement Apoptosis Biology Virus Replication medicine.disease_cause Retinoblastoma Protein Adenoviridae Inhibitor of Apoptosis Proteins Mice Cytopathogenic Effect Viral Cell Line Tumor Interleukin 24 Genetics medicine Animals Humans Promoter Regions Genetic Molecular Biology Cell Proliferation Oncolytic Virotherapy Cell growth Interleukins Interleukin Genetic Therapy Xenograft Model Antitumor Assays Oncolytic virus Oncolytic Viruses Cancer research Molecular Medicine Microtubule-Associated Proteins |
| Zdroj: | Human Gene Therapy. 20:818-830 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.2008.205 |
| Popis: | Interleukin (IL)-24 is an excellent therapeutic gene for cancer therapy. In this work, IL-24 was inserted into Ad.sp-E1A(Delta24), an oncolytic adenovirus with a 24-bp deletion in the E1A gene, which was driven by the survivin promoter to form Ad.sp-E1A(Delta24)-IL-24. Ad.sp-E1A(Delta24)-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(Delta24)-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(Delta24)-IL-24 with such an excellent, broad, and specific antitumor effect in vitro and nearly complete inhibition of lung tumor growth in vivo. |
| Databáze: | OpenAIRE |
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