雷公藤内酯醇对多发性骨髓瘤KM3细胞增殖与凋亡和H3K4me3蛋白表达的影响  

Effect of triptolide on the proliferation, apoptosis and and H3K4me3 protein expression in multiple myeloma KM3 cell

作　　者：邵燕萍[1,2] 罗文达[2] 郭群依[2] 蔡真[1] 

机构地区：[1]浙江大学附属第一医院血液科,杭州310003 [2]台州医院血液科,浙江台州317000

出　　处：《中国临床药理学杂志》2015年第17期1757-1759,1785,共4页The Chinese Journal of Clinical Pharmacology

基　　金：浙江省医药卫生科技计划基金资助项目(KYB345)

摘　　要：目的探讨雷公藤内酯醇对多发性骨髓瘤KM3细胞增殖、凋亡和组蛋白3第4位赖氨酸的三甲基化(H3K4me3)蛋白表达的影响。方法以人多发性骨髓瘤细胞株KM3为研究对象,用噻唑蓝(MTT)法检测细胞增殖活性;Annexin V-FITC/PI双标流式细胞术和共聚焦显微镜检测细胞凋亡;蛋白质印迹法和共聚焦显微镜检测雷公藤内酯醇对KM3细胞H3K4me3表达的影响。结果雷公藤内酯醇对KM3细胞的增殖有明显抑制作用,呈现剂量和时间依赖关系(P<0.05)。雷公藤内酯醇对KM3细胞有明显诱导凋亡的作用,并且随着雷公藤内酯醇作用浓度的增加,细胞凋亡比例逐渐增加,其中总凋亡率分别为(48.97±1.78)%,(53.72±2.21)%和(60.75±2.43)%。H3K4me3集中分布于细胞核内,80 nmol·L-1雷公藤内酯醇干预48 h后,KM3细胞H3K4me3的平均荧光强度值(21.96±0.34)显著低于对照组(39.86±0.47)(P<0.05)。结论雷公藤内酯醇可抑制多发性骨髓瘤KM3细胞增殖,诱导KM3细胞凋亡,降低H3K4me3蛋白表达。Objective To investigate the effect of triptolide on the proliferation,apoptosis and and H3K4me3 protein expression in multiple myeloma KM3 cell. Methods The MM KM3 cell line was cultured with triptolide. Cell proliferation was detected by MTT method. Apoptosis was evaluated by Annexin- V- FITC / PI- labeled flow cytometry and confocal microscopy. The expression of H3K4me3 in KM3 cells was assayed by Western blotting and confocal microscopy. Results Triptolide had obvious inhibition on proliferation of KM3 cells and showed a dose and time dependence. Triptolide had obvious inhibition on apoptosis of KM3 cells,and with the increase of triptolide concentration,the apoptosis ratio increased gradually. The the total apoptosis rates were（ 48. 97 ± 1. 78） %,（ 53. 72 ± 2. 21） % and（ 60. 75 ± 2. 43） %.Confocal laser scanning microscopy showed H3K4me3 accumulated in the nucleus,after 48 h intervention of 80 nmol·L- 1of triptolide,the mean value of fluorescence intensity of H3K4me3 in KM3 cells（ 21. 96 ＋ 0. 34） was significantly lower than that in the control group（ 39. 86 ± 0. 47）（ P〈 0. 05）. Conclusion Triptolide inhibited cellproliferation,induced cell apoptosis,reduced the expression of H3K4me3 protein.

关 键 词：多发性骨髓瘤 雷公藤内酯醇 KM3 组蛋白3第4位赖氨酸的三甲基化 增殖 凋亡 

分 类 号：R733.3[医药卫生—肿瘤] R979.5[医药卫生—临床医学]