Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells.
Proteasome inhibitor PSI induces apoptosis in human mesothelioma cells.
复制标题
蛋白酶体抑制剂 PSI 诱导人间皮瘤细胞凋亡。
DOI：
10.1016/j.canlet.2005.02.022
复制
发表时间：
2006
期刊：
影响因子：
9.7
通讯作者：
K. Dobra
中科院分区：
文献类型：
--
作者：
Xiaojuan Sun;M. Gulyás;A. Hjerpe;K. Dobra
恶性间皮瘤是一种越来越常见的肿瘤，死亡率几乎为100%。常规治疗无效。我们先前已经用抑制消减杂交和基因芯片技术证明，上皮样间皮瘤细胞系中蛋白酶体的mRNA表达水平高于肉瘤样细胞系。本研究评估了蛋白酶体抑制剂对这两种间皮瘤亚系的不同凋亡作用。蛋白酶体抑制剂在体外和体内的一些肿瘤细胞中显示出显著的抗肿瘤活性，但对间皮瘤细胞的作用尚未研究。间皮瘤细胞的活力降低剂量和时间依赖性的方式由蛋白酶体抑制剂测试; PSI是有效的低剂量，但需要更高的浓度钙蛋白酶抑制剂I。上皮样间皮瘤细胞对抑制剂的敏感性高于肉瘤样间皮瘤细胞，PSI作用24小时的IC_（50）分别为4 μ m和16μm。其他间皮瘤细胞系显示类似的敏感性。PSI似乎通过诱导细胞凋亡来降低间皮瘤的生存能力，这一点通过细胞形态学、半胱天冬酶3裂解的蛋白质印迹分析和流式细胞术分析来验证。总之，PSI，一个代表性的代理，降低生存能力和诱导间皮瘤细胞凋亡，可能是有用的间皮瘤，特别是上皮样表型的患者的治疗。
Malignant mesothelioma is an increasingly common tumor with an almost 100% mortality rate. It is refractory to conventional treatment. We have previously shown with SSH and microarray that the mRNA expression level of proteasome is higher in epithelioid mesothelioma cell lines than in sarcomatoid ones. This study evaluates the differential apoptotic effect of proteasome inhibitors on both of these mesothelioma sub-lines. Proteasome inhibitors show substantial anti-tumor activity in some tumor cells in vitro and in vivo, but the effects on mesothelioma cells has not been studied. The viability of mesothelioma cells was reduced in a dose- and time-dependent manner by the proteasome inhibitors tested; PSI was effective with a low dose, but higher concentrations were needed for calpain inhibitor I. The epithelioid mesothelioma cells are more sensitive to the inhibitors than the sarcomatoid ones, their IC50after 24h of treatment with PSI being 4 and 16μm, respectively. Other mesothelioma cell lines show similar sensitivity. PSI seemed to decrease mesothelioma viability by inducing apoptosis, as verified by cell morphology, Western blotting analysis of caspase 3 cleavage, and flow-cytometric analysis. In conclusion, PSI, a representative agent that reduces viability and induces apoptosis of mesothelioma cells, might be useful in the treatment of patients with mesothelioma, especially of epithelioid phenotype.
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DOI：
--
发表时间：
1998
期刊：
Cancer research.
影响因子：
--
作者：
Orlowski,RZ;Eswara,JR;Lafond-Walker,A;Grever,MR;Orlowski,M;Dang,CV
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Dang,CV
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DOI：
10.1159/000468688
发表时间：
1993
期刊：
Enzyme & protein
影响因子：
--
作者：
Wilk,S;Figueiredo-Pereira,ME
通讯作者：
Figueiredo-Pereira,ME
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影响因子：
3.9
作者：
Figueiredo-Pereira,ME;Chen,WE;Yuan,HM;Wilk,S
通讯作者：
Wilk,S
影响因子：
3.9
作者：
Korsmeyer, KK;Davoll, S;Correia, MA
通讯作者：
Correia, MA