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表达凋亡素的双肿瘤特异性溶瘤腺病毒对前列腺癌的强效生长抑制作用。

Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma.

机构信息

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun 130031, P.R. China.

出版信息

Int J Oncol. 2013 Mar;42(3):1052-60. doi: 10.3892/ijo.2013.1783. Epub 2013 Jan 21.

DOI:10.3892/ijo.2013.1783
PMID:23338489
Abstract

Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in various human tumor cells, but not in normal cells. To explore the use of apoptin in tumor gene therapy, we assessed a recombinant adenovirus expressing the apoptin protein (Ad-hTERTp-E1a-Apoptin) in order to determine its lethal and growth-inhibitory effects on PC-3 and RM-1 cells in vitro and its antitumor effect on solid tumors in vivo. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), acridine orange (AO)/ethidium bromide (EB), 4'-6-diamidino-2-phenylindole (DAPI), and Annexin V assays showed that Ad-hTERTp-E1a-Apoptin inhibited the proliferation of PC-3 and RM-1 cells in vitro by inducing apoptosis of prostate cancer cells, and that this inhibitory effect was dose and time-dependent. In the animal models, Ad-hTERTp-E1a-Apoptin significantly inhibited tumor growth and extended the lifespan of animals. Experimental results indicate that Ad-hTERTp-E1a-Apoptin has a potential application in tumor gene therapy.

摘要

凋亡素是一种源自禽白血病病毒的、不依赖 p53 的、抗 bcl-2 的凋亡蛋白,能够特异性地诱导各种人类肿瘤细胞凋亡,而对正常细胞无作用。为了探索凋亡素在肿瘤基因治疗中的应用,我们评估了一种表达凋亡素蛋白的重组腺病毒(Ad-hTERTp-E1a-Apoptin),以确定其在体外对 PC-3 和 RM-1 细胞的致死和生长抑制作用,以及在体内对实体瘤的抗肿瘤作用。3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(MTT)、吖啶橙(AO)/溴化乙锭(EB)、4'-6-二脒基-2-苯基吲哚(DAPI)和 Annexin V 检测显示,Ad-hTERTp-E1a-Apoptin 通过诱导前列腺癌细胞凋亡,抑制 PC-3 和 RM-1 细胞的体外增殖,且这种抑制作用呈剂量和时间依赖性。在动物模型中,Ad-hTERTp-E1a-Apoptin 显著抑制肿瘤生长并延长了动物的寿命。实验结果表明,Ad-hTERTp-E1a-Apoptin 在肿瘤基因治疗中有潜在的应用价值。

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