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重组腺病毒 IL-24-Bax 促进肝癌细胞的体外和体内凋亡。

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

机构信息

Molecular Oncology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

出版信息

Cancer Gene Ther. 2010 Nov;17(11):771-9. doi: 10.1038/cgt.2010.34. Epub 2010 Jul 2.

DOI:10.1038/cgt.2010.34
PMID:20596089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2963730/
Abstract

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.

摘要

基因治疗有望成为肝癌治疗的另一种选择。在许多癌症中，已有研究报告表明腺病毒载体传递嵌合蛋白可诱导细胞凋亡。本研究旨在评估重组腺病毒白细胞介素（IL）-24-Bax 是否能在体外和体内诱导肝癌细胞凋亡。构建了几种重组腺病毒，并测量了其编码蛋白的表达。通过细胞活力和凋亡测定，研究了重组腺病毒对肝癌细胞和正常肝细胞系的影响，细胞在 Ad.Luc、Ad.IL-24、Ad.Bax 或 Ad.IL-24-Bax 处理后。还探讨了涉及的机制。使用荷瘤小鼠模型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细胞凋亡，但对正常肝细胞影响不大。这种反应的机制可能包括 10HRE/VEGF385 启动子的作用和 IL-24 和 Bax 的协同作用。Ad.IL-24-Bax 还抑制裸鼠肿瘤生长并诱导细胞凋亡。Ad.IL-24-Bax 可能是肝癌基因治疗的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/1154c6bfe471/cgt201034f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/848b4862e792/cgt201034f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/b827e0bdea0f/cgt201034f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/7ec84039cc3d/cgt201034f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/407ef0215984/cgt201034f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/79d602cd8d99/cgt201034f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/1154c6bfe471/cgt201034f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/848b4862e792/cgt201034f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/b827e0bdea0f/cgt201034f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/7ec84039cc3d/cgt201034f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/407ef0215984/cgt201034f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/79d602cd8d99/cgt201034f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fbb/2963730/1154c6bfe471/cgt201034f6.jpg

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