目的 探讨苦参碱对人大肠癌HT29细胞增殖抑制和凋亡诱导作用及其可能机制。方法 分别采用MTT法检测细胞增殖活性、流式细胞仪检测细胞周期及凋亡、透射电镜观察细胞结构变化、基因芯片检测细胞基因表达改变。结果 0.0625～0.5mg/mL苦参碱处理48h后,细胞增殖明显受抑制;但1mg/mL时增殖抑制率降低而凋亡诱导作用明显增强;苦参碱对细胞G2/M和G1/S期均有阻滞作用;电镜下可见凋亡的形态学变化;基因芯片检测发现苦参碱影响细胞增殖、周期和凋亡相关基因的表达。结论 苦参碱通过影响HT29细胞一些与增殖、周期和凋亡相关基因的表达发挥增殖抑制和凋亡诱导作用,且与苦参碱质量浓度相关。

Objective To explore the anti-proliferation and apoptosis-induced effects of matrine on HT29 cell and their possible mechanism.Methods HT29 Cell proliferative activity was measured by MTT assay;Cell cycle and apoptosis were analyzed by Flow Cytometry;Alteration of cellular skeleton was observed by transmission electron microscopy(TEM);Global gene expression profiles were scanned by gene chip.Results After exposure to matrine at concentrations from 0.062 5 to 0.5 mg/mL for 48 h,cellular proliferation was inhibited with increasing the concentration,but this inhibitory effect attenuated at 1 mg/mL and the apoptosis was up-regulated significantly.G2/M and G1/S phases of cell cycle were,to some extent,arrested.Under TEM,the morphological changes could be found.Gene chip showed that matrine could alter a large number of genes,which related to the cell proliferation,cell cycle,and apoptosis.Conclusion The anti-proliferation and apoptosis-induced effects of matrine on HT29 cells are concentration-dependent through changing of many genes involved in proliferation,cell cycle,and apoptosis.

浙江省自然科学基金青年人才专项基金资助项目(R01055);浙江省中医药管理局资助课题(2003C094,2006Z012)