Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model
Inhibition of ovarian cancer metastasis by adeno-associated virus-mediated gene transfer of nm23H1 in an orthotopic implantation model
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DOI：
10.1038/sj.cgt.7700899
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发表时间：
2006-03-01
影响因子：
6.4
通讯作者：
Ma, D
中科院分区：
文献类型：
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作者：
Li, J;Zhou, J;Ma, D
卵巢癌是女性中最具威胁性的恶性肿瘤之一，因其在诊断前经常发生转移。本研究探讨了通过腺相关病毒（adeno-associated virus， AAV）介导的基因转移促进nm23H1表达预防卵巢癌转移的可能性。通过体内筛选获得一株具有高转移潜力的细胞系SW626-M4，并用于建立小鼠卵巢癌转移模型。将表达nm23H1的重组腺相关病毒载体（AAV-nm23H1）转移至上述模型后，检测肝脏转移和动物存活时间。将AAV-nm23H1腹腔注射到卵巢癌原位植入模型中，(1)95%以上的裸鼠肿瘤细胞原位表达外源基因；(2)发生肝转移的动物数量减少60%；(3)与未处理宿主组相比，中位生存时间延长35天。总之，这些结果支持通过基因转移诱导nm23H1表达作为预防转移和延长宿主生存时间的治疗策略的可行性，并表明在未来的基因治疗方法设计中，AAV载体值得关注，以实现治疗基因在体内的长期表达。
Ovarian cancer is one of the most threatening malignant tumors in females due to the frequent occurrence of metastasis that precedes diagnosis. The present study explored the possibility of preventing ovarian cancer metastasis by promoting nm23H1 expression through adeno-associated virus (AAV)-mediated gene transfer. A cell line of high metastatic potential, SW626-M4, was derived by in vivo selection and used to establish an ovarian cancer metastasis model in the mouse. Liver metastasis and animal survival time were measured after transfer of a recombinant adeno-associated viral vector expressing nm23H1 (AAV-nm23H1) into the aforementioned model. Intraperitoneal injection of AAV-nm23H1 into this orthotopic implantation model of ovarian cancer resulted in (1) expression of the exogenous gene in more than 95% of tumor cells in situ in nude mice; (2) a 60% reduction in the number of animals developing liver metastases; and (3) a 35-day prolongation of median survival time compared with the untreated host group. In conclusion, the results support the feasibility of induction of nm23H1 expression through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival time, and indicate that AAV vectors deserve attention in the design of future gene therapy approaches to achieving long-term expression of curative genes in vivo.