Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo

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• 作者：Li Xiao (1)
  Liu Yan (1) (2)
  Wen Zhongmei (1) (3)
  Li Chang (1)
  Lu Huijun (1)
  Tian Mingyao (1)
  Jin Kuoshi (1)
  Sun Lili (4)
  Gao Pegn (1) (5)
  Yang Encheng (1) (2) (6)
  Xu Xiaohong (1) (2) (6)
  Kan Shifu (1)
  Wang Zhuoyue (1)
  Wang Yuhang (1)
  Jin Ningyi (1)
  
• 刊名：Molecular Cancer
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：9
• 期：1
• 全文大小：3272KB
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• 作者单位：Li Xiao (1)
  Liu Yan (1) (2)
  Wen Zhongmei (1) (3)
  Li Chang (1)
  Lu Huijun (1)
  Tian Mingyao (1)
  Jin Kuoshi (1)
  Sun Lili (4)
  Gao Pegn (1) (5)
  Yang Encheng (1) (2) (6)
  Xu Xiaohong (1) (2) (6)
  Kan Shifu (1)
  Wang Zhuoyue (1)
  Wang Yuhang (1)
  Jin Ningyi (1)
  
  1. Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun, China
  2. Department of Gastroenterology, the First Hospital of Jilin University, Changchun, China
  3. Department of Respiratory Medicine, the First Hospital of Jilin University, Changchun, China
  4. Head and Neck Surgery, The Tumor hospital of Jilin province, Changchun, China
  5. Department of Hematology and Oncology, People's Hospital of Jilin Province, Changchun, China
  6. The Hospital of Digestive Diseases, Hospital of Heilongjiang Province, Harbin, China
  
• ISSN：1476-4598

文摘

Background Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. Here, we generated a conditional replication-competent adenovirus (CRCA), designated Ad-hTERT-E1a-Apoptin, and investigated the effectiveness of the CRCA a gene therapy agent for further clinical trials. Results The observation that infection with Ad-hTERT-E1a-Apoptin significantly inhibited growth of the melanoma cells, protecting normal human epidermal melanocytes from growth inhibition confirmed cancer cell selective adenoviral replication, growth inhibition, and apoptosis induction of this therapeutic approach. The in vivo assays performed by using C57BL/6 mice containing established primary or metastatic tumors expanded the in vitro studies. When treated with Ad-hTERT-E1a-Apoptin, the subcutaneous primary tumor volume reduction was not only observed in intratumoral injection group but in systemic delivery mice. In the lung metastasis model, Ad-hTERT-E1a-Apoptin effectively suppressed pulmonary metastatic lesions. Furthermore, treatment of primary and metastatic models with Ad-hTERT-E1a-Apoptin increased mice survival. Conclusions These data further reinforce the previously research showing that an adenovirus expressing Apoptin is more effective and advocate the potential applications of Ad-hTERT-E1a-Apoptin in the treatment of neoplastic diseases in future clinical trials.