Wang Xiao-Ping, Chen Tong-Sheng, Sun Lei, Cai Ji-Ye, Wu Ming-Qian, Mok Martin
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, China.
Micron. 2008 Dec;39(8):1216-21. doi: 10.1016/j.micron.2008.04.007. Epub 2008 Apr 26.
Taxol (paclitaxel), one of the most active cancer chemotherapeutic agents, can cause programmed cell death (PCD) and cytoplasmic vacuolization. The objective of this study was to analyze the morphological characteristics induced by taxol. Human lung adenocarcinoma (ASTC-a-1) cells were exposed to various concentration of taxol. CCK-8 was used to assay the cell viability. Atomic force microscopy (AFM), plasmid transfection and confocal fluorescence microscopy were performed to image the cells morphological change induced by taxol. Fluorescence resonance energy transfer (FRET) was used to monitor the caspase-3 activation in living cells during taxol-induced cell death. Cells treated with taxol exhibited significant swelling and cytoplasmic vacuolization which may be due to endoplasmic reticulum (ER) vacuolization. Caspase-3 was not activated during taxol-induced cytoplasmic vacuolization and cell death. These findings suggest that taxol induces caspase-3-independent cytoplasmic vacuolization, cell swelling and cell death through ER vacuolization.
紫杉醇(paclitaxel)是最有效的癌症化疗药物之一,可导致程序性细胞死亡(PCD)和细胞质空泡化。本研究的目的是分析紫杉醇诱导的形态学特征。将人肺腺癌(ASTC-a-1)细胞暴露于不同浓度的紫杉醇中。使用CCK-8测定细胞活力。采用原子力显微镜(AFM)、质粒转染和共聚焦荧光显微镜对紫杉醇诱导的细胞形态变化进行成像。利用荧光共振能量转移(FRET)监测紫杉醇诱导细胞死亡过程中活细胞内半胱天冬酶-3的激活情况。用紫杉醇处理的细胞表现出明显的肿胀和细胞质空泡化,这可能是由于内质网(ER)空泡化所致。在紫杉醇诱导的细胞质空泡化和细胞死亡过程中,半胱天冬酶-3未被激活。这些发现表明,紫杉醇通过内质网空泡化诱导不依赖半胱天冬酶-3的细胞质空泡化、细胞肿胀和细胞死亡。