白藜芦醇对多发性骨髓瘤细胞的增殖抑制作用及相关机制研究  

Inhibitory Effect of Resveratrol on the Proliferation of Multiple Myeloma Cells and the Underlying Mechanism

作　　者：周楠 曹舒兴[2] 王真真 罗建民[1] 刘小军[1] 尚银涛[1] 杨琳[1] ZHOU Nan;CAO Shu-Xing;WANG Zhen-Zhen;LUO Jian-Min;LIU Xiao-Jun;SHANG Yin-Tao;YANG Lin(Department of Hematology,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;Department of Orthopedics,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学第二医院血液科,河北石家庄050000 [2]河北医科大学第二医院骨科,河北石家庄050000

出　　处：《中国实验血液学杂志》2023年第4期1093-1099,共7页Journal of Experimental Hematology

摘　　要：目的:探讨白藜芦醇(resveratrol,RSV)对多发性骨髓瘤(MM)细胞增殖的影响及其分子机制。方法:不同浓度的RSV作用于MM细胞(MM1.S、RPMI-8226和U266)24-72 h,CCK-8法检测RSV对MM细胞增殖的影响;将RPMI-8226细胞分为RSV、miR-21 mimic、RSV+miR-21 mimic、miR-21 inhibitor和RSV+miR-21 inhibitor组,转染相应的质粒,碘化丙啶单染流式细胞术检测各组细胞的周期分布,Annexin V-FITC/PE-PI双染法观察各组细胞的凋亡情况,q RT-PCR技术检测RSV处理后MM细胞中miR-21的表达水平和各组细胞中的KLF5 miRNA表达水平,Western blot技术检测各组细胞中的KLF5蛋白的表达水平。结果:RSV呈时间-剂量依赖性抑制MM细胞增殖,诱导细胞凋亡发生;RSV处理MM细胞后,亚G1期细胞增多,G2/M期细胞减少;同时RSV显著下调了MM细胞中miR-21的表达,且给予RSV后抵消了miR-21 mimic对MM细胞中KLF5表达的抑制作用。结论:RSV通过抑制miR-21上调KLF5的表达水平,从而抑制MM细胞增殖并诱导其凋亡的发生。Objective:To investigate the effect of resveratrol(RSV)on the proliferation of multiple myeloma(MM)cells and its molecular mechanism.Methods:MM cells(MM1.S,RPMI-8226 and U266)were treated with different concentrations of RSV for 24-72 h.The effect of RSV on the proliferation of MM cells was detected by CCK-8(cell counting kit-8)assay.RPMI-8226 cells were divided into RSV,miR-21 mimic,RSV+miR-21 mimic,miR-21 inhibitor and RSV+miR-21 inhibitor groups,and transfected with corresponding plasmids.The cell cycle distribution of each group was detected by flow cytometry with propidium iodide(PI)single staining.The cell apoptosis of each group was detected by AnnexinV-FITC/PE-PI double staining.The expression of miR-21 in MM cells treated with RSV and the expression of KLF5 mRNA in each group were detected by qRT-PCR.The expression of KLF5 protein in each group was detected by Western blot.Results:RSV inhibited the proliferation and induced apoptosis of MM cells in a time-and dose-dependent manner.After the MM cells were treated with RSV,the number of cells in sub-G1 phase was increased,and that in G2/M phase was decreased.Moreover,RSV significantly downregulated the expression of miR-21 in MM cells,and the inhibitory effect of miR-21 mimic on KLF5 expression in MM cells was counteracted by RSV.Conclusion:RSV may inhibit the proliferation and induce apoptosis of MM cells by inhibiting miR-21 and up-regulating KLF5 expression.

关 键 词：白黎芦醇 微小RNA 多发性骨髓瘤 增殖 凋亡 

分 类 号：R733.3[医药卫生—肿瘤]