紫杉醇诱导人乳腺癌M CF-7细胞周期阻断及凋亡的基因表达谱分析(英文)

Differential gene expression profiles in paclitaxel-induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells

目的研究紫杉醇诱导人MCF-7细胞周期阻断及凋亡的分子机制。方法用流式细胞仪分析紫杉醇对MCF-7细胞周期变化的影响,用自制的含9 984个已知基因和EST的高密度基因芯片检测MCF-7细胞在不同浓度紫杉醇作用下的基因表达变化。结果MCF-7细胞在100 nmol.L-1紫杉醇作用24 h,流式细胞仪结果显示77.8%细胞阻断在G2/M期和1.3%细胞发生凋亡;基因表达谱分析发现:在12.5 nmol.L-1(IC50)及100 nmol.L-1紫杉醇作用下,分别有27及77个基因差异表达。结论紫杉醇可诱导MCF-7细胞周期阻断在G2/M期并引起部分细胞凋亡,该作用与药物浓度有关。基因表达谱分析显示部分差异表达基因参与细胞微管及骨架结构、细胞周期调控、以及DNA损伤修复和凋亡过程。

Aim To elucidate the molecular mechanism of cell cycle arrest and apoptosis of MCF-7 cells induced by paclitaxel. Methods Flow cytometry was used to determine the cell cycle changes of MCF-7 cells upon paclitaxel treatment. Gene expression profiles of MCF-7 cells induced by paclitaxel were obtained by using cDNA microarrays containing 9 984 genes and expressed sequence tags （ESTs）.Results Cell cycle analysis showed that 77.8% of cells arrested at G2/M phase and 1.3% of cells caused G2/M cell cycle arrest and apoptotic cell death in a concentration-dependent manner, which is associated with the regulation of selected genes related to microtubule assembly and cytoskeleton, cell cycle regulation, and DNA repair and apoptosis.