Roussel Elise, Bélanger Martin M, Couet Jacques
Unité de Recherche en Pneumologie, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Centre de Recherche Hôpital Laval, Université Laval, Sainte-Foy (Québec), Canada.
Anticancer Drugs. 2004 Nov;15(10):961-7. doi: 10.1097/00001813-200411000-00005.
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.
小窝蛋白在终末分化细胞中高表达，但在各种癌细胞系中这种表达会下调。暴露于低剂量的紫杉醇（泰素）足以上调小窝蛋白-1，这表明轻度的细胞毒性应激会引发一种涉及小窝蛋白和小窝的反应。在此我们表明，即使在紫杉醇治疗停止后，这种上调仍会持续。在暴露于细胞生长抑制剂量的紫杉醇（50 nM）后，A549肺癌细胞被阻滞在G2/M细胞周期阶段。去除紫杉醇后，细胞死亡发生，同时小窝蛋白表达增加，这表明小窝蛋白在此过程中发挥了作用。紫杉醇治疗三天后，存活的A549细胞传代，其中只有一半能贴附于培养皿。贴附的细胞（仍主要处于G2/M细胞周期阶段）仍无法生长，并逐渐进入凋亡状态。这项研究表明，即使在药物去除1周后，低剂量紫杉醇的影响仍然存在，并且小窝蛋白-1是细胞毒性的一个良好标志物。
