| 依托泊苷通过蛋白酶体通路诱导白血病细胞凋亡 |
| 投稿时间：2009-09-17 修订日期：2009-10-20 点此下载全文 |
| 引用本文：叶齐,王婧,郭学青,陈崇宏,张俊平.依托泊苷通过蛋白酶体通路诱导白血病细胞凋亡[J].药学实践杂志,2010,28(1):25~28,69 |
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| 基金项目:国家自然科学基金资助项目(30472032) |
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| 中文摘要:目的研究拓扑异构酶Ⅱ抑制剂依托泊苷诱导白血病细胞HL-60凋亡的分子机制。方法细胞增殖和凋亡采用四唑氮盐(MTT)法和流式细胞仪测定,基因芯片技术检测依托泊苷作用于HL-60细胞2 h后基因表达谱的变化。应用Gen-MAPP分析软件分析细胞内反应通路。结果依托泊苷半数抑制浓度(IC50)为(30.17±0.26)μmol/L。依托泊苷促进HL-60细胞凋亡,凋亡百分率由对照组4.38%增加到药物处理组的53.96%,能显著抑制细胞内蛋白酶体降解通路(Z≥3.8),抑制蛋白酶体通路中的PSMB5、PSMB7、PSMB8、PSMC3、PSMC5、RPN1和HLA-A表达。结论依托泊苷抑制DNA拓扑异构酶II可通过抑制细胞内蛋白酶体相关基因表达导致细胞凋亡。 |
| 中文关键词:依托泊苷 白血病细胞 蛋白酶体 基因芯片 |
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| Etoposide induces apoptosis via ubiquitin-proteasome pathway in HL-60 leukemia cells |
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| Abstract:Objective To investigate the molecular mechanisms of Topoisomerase II inhibitor etopside(induced apoptosis on human leukemia HL-60 cells.Methods Cell growth and apoptosis were determined by MTT assay and flow cytometry.cDNA microarray was used to assess sensitive early gene expression profiles and Genmapp software was used to gene cluster and pathway analysis of the drug response.Results Etopside exhibited cell growth inhibition by 50 % at the concentrations of(30.17±0.26)mol/L and induced cell apoptosis from 4.38% to 53.96%.Genmapp analysis showed that etopside significantly inhibited ubiquitin-proteasome pathway(Z≥3.8) and decreased expression of genes involved in ubiquitin-proteasome pathway(PSMB5、PSMB7、PSMB8、PSMC3、PSMC5、RPN1and HLA(A).Conclusion Etoposide induces apoptosis via decreased expression of genes in ubiquitin-proteasome pathway. |
| keywords:etopside leukemia cells proteasome cDNA microarray |
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