Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim
Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim
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DOI：
10.1038/sj.cdd.4401554
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发表时间：
2005-03-01
影响因子：
12.4
通讯作者：
Hu, HM
中科院分区：
文献类型：
--
作者：
Li, R;Moudgil, T;Hu, HM
在一组短期培养的非小细胞肺癌（NSCLC）细胞系中观察到对紫杉醇介导的杀伤的敏感性的显著变化。对紫杉醇杀伤的敏感性与仅BH 3蛋白Bim的表达相关，但与Bcl-2家族的其他成员无关。具有最高水平Bim表达的NSCLC细胞系在紫杉醇处理后对凋亡诱导最敏感。Bim的强制表达增加了紫杉醇介导的对表达不可检测水平的Bim的细胞的杀伤。相反，敲低Bim，而不是Bcl-2的表达，降低了肿瘤细胞对紫杉醇介导的杀伤的敏感性。使用一组乳腺癌和前列腺癌细胞系进行了类似的观察。紫杉醇损害微管功能，导致G2/M细胞周期阻滞，线粒体损伤和p53非依赖性细胞凋亡。这些结果确立了Bim作为微管毒物紫杉醇和细胞凋亡之间的关键分子联系。
A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level of Bim expression are most susceptible to apoptosis induction after paclitaxel treatment. Forced expression of Bim increased paclitaxel-mediated killing of cells expressing an undetectable level of Bim. Conversely, knock down of Bim, but not Bcl-2 expression, decreased the susceptibility of tumor cells to paclitaxel-mediated killing. Similar observations were made using a panel of breast and prostate cancer cell lines. Paclitaxel impairs microtubule function, causes G2/M cell cycle blockade, mitochondria damage, and p53-independent apoptosis. These results established Bim as a critical molecular link between the microtubule poison, paclitaxel, and apoptosis.