A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells
A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells
复制标题
survivin双点突变体对肝癌细胞的生长具有强效抑制作用
DOI：
10.4161/cbt.7.4.5484
复制
发表时间：
2008-04
影响因子：
3.6
通讯作者：
Qin, Wei Wei
中科院分区：
文献类型：
--
作者：
Wang, Kai;Zhang, Rui;Yao, Li Bo;Jia, Lin Tao;Li, Kai Nan;Chen, Rui;Meng, Yan Ling;Yang, An Gang;Zhao, Jing;Wen, Wei Hong;Wang, Tao;Qin, Wei Wei
生存素是癌症治疗中一个有吸引力的靶点。先前的研究表明，生存素显性失活突变体T34A和C84A能够诱导癌细胞凋亡。鉴于它们具有不同的诱导细胞凋亡的机制，我们的研究旨在确定生存素双点突变体（TC34，84AA）是否能够对肝细胞癌细胞的生长产生更有效的抑制作用。构建表达生存素突变体的腺病毒并转导至肝细胞癌细胞中。测量了存活蛋白突变体对癌细胞生长的抑制作用。用所有三种存活蛋白突变体转导癌细胞导致显着的细胞凋亡。与单独的survivin突变体T34A或C84A相比，survivin TC34,84AA的杀癌作用更强。此外，生存素突变体比野生型生存素对泛素-蛋白酶体途径的降解更敏感。我们的结果表明，腺病毒传递的显性失活存活蛋白 TC34,84AA 促进细胞凋亡介导的肝细胞癌抑制，并可能成为癌症治疗的有希望的候选者。
Survivin is an attractive target in cancer therapy. Previous studies have demonstrated that survivin dominant-negative mutants T34A and C84A were able to induce apoptosis in cancer cells. Given that they had different mechanisms in inducing apoptosis, our study was undertaken to determine whether a survivin double point mutant (TC34,84AA) could achieve more potent inhibitory effect on the growth of hepatocellular cancer cells. Adenoviruses expressing survivin mutants were constructed and transduced into hepatocellular cancer cells. The inhibitory effect of the survivin mutants on cancer cell growth was measured. Transduction of cancer cells with all three survivin mutants resulted in significant apoptosis. Compared with survivin mutants T34A or C84A alone, the cancer killing effect of survivin TC34,84AA was much stronger. In addition, the survivin mutants were more sensitive than wild type survivin to the degradation in the ubiquitin-proteasome pathway. Our results suggest that adenovirus-delivered dominant-negative survivin TC34,84AA promotes apoptosis-mediated hepatocellular carcinoma suppression, and could potentially be a promising candidate for cancer therapies.
登录
查看更多内容
影响因子：
81.5
作者：
Llovet, Josep M.;Zucman-Rossi, Jessica;Gores, Gregory
通讯作者：
Gores, Gregory
影响因子：
4
作者：
Jian Zhao;T. Tenev;Luis M. Martins;Julian Downward;N. R. Lemoine
通讯作者：
Jian Zhao;T. Tenev;Luis M. Martins;Julian Downward;N. R. Lemoine
影响因子：
5.1
作者：
Marrero, Jorge A;Pelletier, Shawn
通讯作者：
Pelletier, Shawn
影响因子：
1.5
作者：
Gilles, HoChong;Garbutt, Tonora;Landrum, Jasmine
通讯作者：
Landrum, Jasmine
DOI：
10.1016/s0015-6264(78)80335-6
发表时间：
1986
期刊：
The New Zealand medical journal
影响因子：
--
作者：
D. Woodfield
通讯作者：
D. Woodfield