雷公藤内酯酮对来那度胺原发耐药RPMI-8226细胞增殖及凋亡的影响  

Effect of triptonide on the proliferation and apoptosis of primary lenalidomide-resistant RPMI-8226 cells

作　　者：王家敏 汪玉洁 唐欣欣 戴敏 高安慧 WANG Jia-min;WANG Yu-jie;TANG Xin-xin;DAI min;GAO An-hui(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012;Yangtze Delta Drug Advanced Research Institute,Nantong Jiangsu 226133;Biopolar Hongye(Nantong)Pharmaceutical Co.,Ltd.,Nantong Jiangsu 226126)

机构地区：[1]安徽中医药大学药学院,合肥230012 [2]长三角药物高等研究院,江苏南通226133 [3]百极弘烨(南通)医药科技有限公司,江苏南通226126

出　　处：《中南药学》2023年第6期1496-1501,共6页Central South Pharmacy

摘　　要：目的探讨雷公藤内酯酮对来那度胺原发耐药RPMI-8226细胞增殖及凋亡的影响。方法MTS比色法检测来那度胺和雷公藤内酯酮对不同多发性骨髓瘤细胞增殖能力的影响;流式细胞术检测雷公藤内酯酮对RPMI-8226细胞周期与凋亡的影响;Western blot法检测雷公藤内酯酮对RPMI-8226细胞内IKAROS家族锌指蛋白1(IKZF1)和IKAROS家族锌指蛋白3(IKZF3)表达的影响;RT-qPCR法检测雷公藤内酯酮对RPMI-8226细胞内IKZF1、IKZF3基因转录水平的影响。结果来那度胺对不同类型多发性骨髓瘤细胞增殖的作用强度不同,而雷公藤内酯酮对不同类型多发性骨髓瘤细胞增殖均有强效抑制作用,同时可促进来那度胺非敏感的RPMI-8226细胞凋亡,而对细胞周期变化基本无影响。相较于来那度胺,雷公藤内酯酮可剂量依赖性下调RPMI-8226细胞内IKZF1和IKZF3蛋白的表达,进一步RT-qPCR检测显示,雷公藤内酯酮可降低RPMI-8226细胞IKZF1和IKZF3基因的转录水平。结论雷公藤内酯酮可促进来那度胺原发耐药RPMI-8226细胞的凋亡,并且可通过降低来那度胺原发耐药RPMI-8226细胞内IKZF1和IKZF3基因的转录水平来下调相关蛋白的表达,实现对细胞的增殖抑制作用。Objective To explore the effect of triptonide on the proliferation and apoptosis of primary lenalidomide-resistant RPMI-8226 cells.Methods MTS colorimetric assay was used to detect the effect of lenalidomide and triptonide on the proliferation of different multiple myeloma cells.Flow cytometry was used to detect the effect of triptonide on RPMI-8226 cell cycle and apoptosis.Western blot assay was applied to detect the effect of triptonide concentrations on the expression of IKAROS Family Zinc Finger 1(IKZF1)and IKAROS Family Zinc Finger 3(IKZF3)in RPMI-8226 cells.The effect of triptonide on the transcriptional level of IKZF1 and IKZF3 in RPMI-8226 cells was detected by RT-qPCR assay.Results The effect of lenalidomide on the proliferation of different types of multiple myeloma cells varied.Triptonide strongly inhibited the proliferation of different multiple myeloma cells,and also induced primary lenalidomide-resistant RPMI-8226 cells apoptosis but had no effect on the cell cycle.Compared to lenalidomide,triptonide inhibited the expression of IKZF1 and IKZF3 proteins in a dose-dependent manner.RT-qPCR assay showed that triptonide inhibited the transcriptional levels of IKZF1 and IKZF3.Conclusion Triptonide may induce primary lenalidomide-resistant RPMI-8226 cell apoptosis and reduce the expression of related proteins by inhibiting the transcriptional level of IKZF1 and IKZF3 genes in primary lenalidomide-resistant RPMI-8226 cells,therefor inhibiting the proliferation of RPMI-8226 cells.

关 键 词：雷公藤内酯酮 来那度胺耐药 多发性骨髓瘤 RPMI-8226细胞 增殖 凋亡 

分 类 号：R285[医药卫生—中药学]