基因芯片分析显示昆明山海棠有机萃取液经NF- κB及线粒体信号传导途径诱导HL- 60细胞凋亡

目的　研究中草药昆明山海棠 Tripterygium hypoglaucum( THH)有机萃取液诱导人早幼粒白血病 HL-6 0细胞凋亡过程的信号传导通道及分子机制。方法　应用流式细胞仪研究了 THH有机萃取液诱导 HL - 6 0细胞的凋亡过程 ,并应用包含 3 0 0 0人类基因与 EST的基因芯片进行基因表达差异分析。结果　基因芯片杂交结果显示有 16个基因表达发生大于 2倍的显著变化 ,这些基因同细胞生长 ,细胞周期调控 ,细胞分化 ,以及压力反应有关。部分基因在细胞凋亡过程中起关键作用 ,如 Caspase3和 Caspase8。结论　 THH有机萃取液诱导 HL- 6 0细胞凋亡 ,该过程与 NF- κB和线粒体信号传导途径有关。

Organic extract of Tripterygium hypoglaucum induced apoptosis of HL-60 cells through NF-κB and mitochondrial signaling pathways as revealed by cDNA microarray technique

Object To investigate the signaling pathways and molecular mechanism involved in the apoptosis of human promyleocytic leukemia HL-60 cells induced by organic extract of Tripterygium hypoglaucum (THH) root. Methods Cell biological changes during the apoptosis induction were studied by flow cytometry. Molecular mechanism involved in the apoptosis was examined by cDNA microarray technique. Results Flow cytometric study confirmed the induction of apoptosis by the organic extract of THH. The gene expression profiles of HL-60 cells treated by THH were obtained using a cDNA microarray containing 3 000 human genes derived from a leukocyte cDNA library. Sixteen genes identified to be differentially expressed in HL-60 cells can be clustered into groups related to apoptosis (including Caspases 3 and Caspase 8), cell proliferation, cell cycle control and differentiation, and stress response. Conclusion The induced apoptosis of HL-60 cells by THH extract is associated with the up-regulation of several genes (such as NFKBIB, PRG1 and B2M) related to NF-κB and mitochondrial signaling pathways.