Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells.
Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells.
复制标题
美伐他汀诱导 U266 骨髓瘤细胞凋亡和生长抑制。
作者：
J. Jánosi;A. Sebestyén;J. Bocsi;G. Barna;K. Nagy;I. Vályi;L. Kopper
他汀类药物已成功用于治疗高胆固醇血症。此外，体外研究表明他汀类药物可以引发多种肿瘤细胞系的凋亡。在本研究中，我们分析了美伐他汀（一种 HMG-COA 还原酶（甲羟戊酸途径的限速酶）的新型抑制剂）对 U266 人骨髓瘤细胞的影响。美伐他汀诱导的细胞凋亡与半胱天冬酶活性增加和线粒体膜去极化有关。 Bcl-2 mRNA 和蛋白的表达下调，而 Bax 或 Bcl-XL 蛋白的产生没有变化。线粒体程序得到 caspase-8 和 cleaved-Bid 活性的支持。中和死亡配体/死亡受体途径的抗体——TRAIL-R2Fc、抗TNF-α、抗FASL(NOK-1)——均不影响美伐他汀诱导的细胞凋亡。美伐他汀还刺激多聚糖-1 (syndecan-1) 从骨髓瘤细胞表面脱落。美伐他汀的细胞凋亡诱导作用可被视为复杂抗肿瘤方案的潜在参与者。
Statins have been used successfully in the treatment of hypercholesterinaemia. Moreover, in vitro studies have shown that statins can trigger apoptosis in a variety of tumor cell lines. In the present study we analysed the effect of mevastatin--a novel inhibitor of HMG-COA reductase, the rate-limiting enzyme of the mevalonate pathway--on U266 human myeloma cells. Apoptosis induced by mevastatin was associated with increased caspase activity and depolarisation of the mitochondrial membrane. Expression of Bcl-2 mRNA and protein was down-regulated, with no change in Bax or Bcl-XL protein production. The mitochondrial program was supported by caspase-8 and cleaved-Bid activity. None of the antibodies neutralizing the death-ligand/death-receptor pathway--TRAIL-R2Fc, anti-TNF-alpha, anti-FASL(NOK-1)--influenced the mevastatin-induced apoptosis. Mevastatin also stimulated shedding of syndecan-1 from the surface of myeloma cells. The apoptosis inducing effect of mevastatin could be considered as a potential participant in a complex antitumor protocol.
影响因子：
11.2
作者：
Y. Tu;S. Renner;F. Xu;A. Fleishman;J. Taylor;J. Weisz;R. Vescio;M. Rettig;J. Berenson
通讯作者：
Y. Tu;S. Renner;F. Xu;A. Fleishman;J. Taylor;J. Weisz;R. Vescio;M. Rettig;J. Berenson
影响因子：
20.3
作者：
Dhodapkar, MV;Abe, E;Sanderson, RD
通讯作者：
Sanderson, RD