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Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo

机译:重组腺病毒IL-24-Bax在体内外促进肝癌细胞凋亡

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摘要

Gene therapy promises to become an alternative choice for the treatment of hepatic cancer. In many cancers, the delivery of chimeric proteins by adenovirus vector has been reported to induce apoptosis. This study was performed to evaluate whether the recombinant adenovirus interleukin (IL)-24-Bax can induce apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Several recombinant adenoviruses were constructed, and the expression of their encoded proteins was measured. The effects of the recombinant adenovirus on hepatocellular carcinoma cells and the normal hepatocyte cell line were investigated through cell viability and apoptosis assays after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax. The mechanism involved was also explored. A tumor-bearing mouse model was used to evaluate the effects of the adenovirus on tumor volume and cell apoptosis in vivo. Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells and induced apoptosis, but it had little influence on the normal hepatocytes. The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax. Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis. Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.
机译:基因治疗有望成为治疗肝癌的另一种选择。在许多癌症中,已报道通过腺病毒载体递送嵌合蛋白可诱导细胞凋亡。进行这项研究以评估重组腺病毒白介素(IL)-24-Bax是否可以在体外和体内诱导肝癌细胞的凋亡。构建了几种重组腺病毒,并测量了其编码蛋白的表达。用Ad.Luc,Ad.IL-24,Ad.Bax或Ad.IL-24-处理细胞后,通过细胞生存力和凋亡测定研究了重组腺病毒对肝癌细胞和正常肝细胞系的影响。巴克斯还探讨了涉及的机制。荷瘤小鼠模型用于评估腺病毒对体内肿瘤体积和细胞凋亡的影响。 Ad.IL-24-Bax选择性抑制肝癌细胞的生长并诱导凋亡,但对正常肝细胞的影响很小。此反应的机制可能包括10HRE / VEGF385启动子的作用以及IL-24和Bax的协同作用。 Ad.IL-24-Bax也抑制裸鼠的肿瘤生长并诱导凋亡。 Ad.IL-24-Bax可能是用于肝癌基因治疗的有用工具。

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