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首页> 外文期刊>Cancer letters >Suppression of cancer growth in mice by adeno-associated virus vector-mediated IFN-beta expression driven by hTERT promoter.
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Suppression of cancer growth in mice by adeno-associated virus vector-mediated IFN-beta expression driven by hTERT promoter.

机译：通过HTERT启动子驱动的腺相关病毒载体介导的IFN-β表达抑制小鼠癌症生长。

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摘要

Adeno-associated virus (AAV) has rapidly become a promising gene delivery vehicle for its excellent advantages of non-immunogenic, low pathogenicity and long-term gene expression in vivo. However, a major obstacle in development of effective AAV vector is the lack of tissue specificity, which caused low efficiency of AAV transfer to target cells. The application of human telomerase reverse transcriptase (hTERT) promoter is a prior targeting strategy for AAV in cancer gene therapy as hTERT activity is transcriptionally upregulated in most cancer cells. In the present work, we investigated whether AAV-mediated human interferon beta (IFN-beta) gene driven by hTERT promoter could specifically express in tumor cells and suppress tumor cell growth. Our data demonstrated that hTERT promoter-driven IFN-beta expression was the tumor-specific, decreased the cell viability of tumor cells but not normal cells, and induced tumor cell apoptosis via activation of caspase pathway and release of cytochrome c. AAV-mediated IFN-beta expression driven by hTERT promoter significantly suppressed the growth of colorectal cancer and lung cancer xenograft in mice and resulted in tumor cells death in vivo. These data suggested that AAVs in combination with hTERT-mediated IFN-beta expression could exert potential antitumor activity and provide a novel targeting approach to clinical gene therapy of varieties of cancers.
机译：腺相关病毒（AAV）迅速成为非免疫原性，低致病性和长期基因表达的优异优势。然而，有效AAV载体的发展中的主要障碍是缺乏组织特异性，这导致AAV转移到靶细胞的低效率。人端粒酶逆转录酶（HTERT）启动子的应用是癌症基因治疗中AAV的先前靶向策略，因为HTERT活性在大多数癌细胞中转录上调。在本作工作中，我们研究了由HTERT启动子驱动的AAV介导的人干扰素β（IFN-BETA）基因可以在肿瘤细胞中特异性地表达并抑制肿瘤细胞生长。我们的数据表明，HTERT启动子驱动的IFN-β表达是肿瘤特异性的，降低肿瘤细胞但不是正常细胞的细胞活力，并通过激活胱天蛋白途径和释放细胞色素C的肿瘤细胞凋亡。 AAV介导的IFN-β由HTERT启动子驱动的IFN-β表达显着抑制了小鼠中结肠直肠癌和肺癌异种移植物的生长，并导致体内肿瘤细胞死亡。这些数据表明，与HTERT介导的IFN-β表达组合的AAV可以发挥潜在的抗肿瘤活性，并提供一种新的靶向癌症临床基因治疗的靶向方法。

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