G2/M blockade by paclitaxel induces caveolin-1 expression in A549 lung cancer cells: caveolin-1 as a marker of cytotoxicity-猫眼课题宝

紫杉醇阻断 G2/M 诱导 A549 肺癌细胞中的 Caveolin-1 表达：Caveolin-1 作为细胞毒性标志物

DOI：

发表时间：

2004

期刊：

Anti-Cancer Drugs

影响因子：

2.3

通讯作者：

中科院分区：

医学4区

文献类型：

作者：

É. Roussel;Martin M. Bélanger;J. Couet

Caveolins在终末分化的细胞中高表达，但在各种癌细胞系中表达下调。暴露在低剂量紫杉醇(紫杉醇)中足以上调小窝蛋白-1的表达，这表明温和的细胞毒性应激诱导了小窝蛋白和小窝蛋白的反应。我们在这里表明，即使在紫杉醇停止治疗后，这种上调仍然持续。A549肺癌细胞暴露于紫杉醇(50 NM)抑制剂量后，细胞周期被阻断在G2/M期。去除紫杉醇后，细胞死亡，同时小窝蛋白表达增加，提示小窝蛋白在这一过程中起作用。紫杉醇作用3天后，存活的A549细胞传代，只有一半细胞贴壁在培养皿上。贴壁细胞(主要仍处于G2/M期)仍不能生长，并逐渐进入凋亡状态。这项研究表明，即使在撤药一周后，小剂量紫杉醇的作用仍然存在，小窝蛋白-1是细胞毒性的良好标志。

Caveolins are highly expressed in terminally differentiated cells, but this expression is down-regulated in various cancer cell lines. Exposure to low doses of paclitaxel (taxol) is sufficient to up-regulate caveolin-1, suggesting that a mild cytotoxic stress induces a response implying caveolin and caveolae. Here we show that this up-regulation is sustained even after the cessation of paclitaxel treatment. After exposure to a cytostatic dose of paclitaxel (50 nM), A549 lung cancer cells are blocked in the G2/M cell cycle phase. After removal of paclitaxel, cell death occurs, accompanied with an increase in caveolin expression, suggesting an effect of caveolin in this process. Three days post-paclitaxel treatment, surviving A549 cells were passaged and only a half of them adhered to the culture dish. Adhering cells (still mainly in the G2/M cell cycle phase) were still unable to grow and progressively entered in an apoptotic state. This study suggests that effects of a low dose of paclitaxel were still present even 1 week after drug removal and that caveolin-1 is a good marker of cytotoxicity.