和厚朴酚联合三氧化二砷诱导骨髓瘤细胞凋亡的作用机制

The Effect of Proliferation Inhibition on RBMI8226 Cells by Combining Honokiol with Arsenic Trioxide

目的:探究和厚朴酚(HNK)联合三氧化二砷(As2O3)诱导人多发性骨髓瘤RBMI8226细胞株的凋亡作用机制。方法:不同浓度的HNK、As2O3单药作用于细胞24 h、48 h、72 h后,采用CCK-8法检测细胞增殖抑制率;应用AnnexinV-FITC/PI双染及PI单染法流式细胞术检测各处理组细胞凋亡和周期分布情况;采用Western blot法检测细胞中Bcl-2、Bax、Caspase-3蛋白表达水平。结果:HNK与As2O3单药对RBMI8226细胞增殖具有抑制作用,呈时间和剂量依赖性;HNK与As2O3单药能有效诱导细胞凋亡,两药联合后对细胞的诱导凋亡作用较单药显著,差异具有统计学意义(P<0.05);HNK和As2O3单药可使骨髓瘤细胞阻滞在S期,两药联合可增强诱导细胞分化作用,使细胞由G1、G2期进入S期,差异具有统计学意义(P<0.01)。联合用药时能够降低细胞的Bcl-2水平、增加Caspase-3以及BAX水平表达。结论:HNK及As2O3联合对人多发性骨髓瘤RBMI8226细胞株具有协同杀伤作用,该作用可能通过激活凋亡相关信号通路来诱导凋亡。

Objective To explore the potential mechanism of honokiol combined with arsenic trioxide on proliferation to Multiple myeloma RBMI8226 cells.Methods After different concentrations of HNK and As2O3 acted on the cells for 24 h,48 h,72 h,the cell proliferation inhibition rate was detected by the CCK-8 method;the AnnexinV-FITC/PI double staining and PI single staining method were used for flow cytometry detection of apoptosis and cycle distribution for each group;Western blot was used to detect the expression levels of Bcl-2,Bax,and Caspase-3 proteins in the cells.Results The inhibitory effects of honokiol and arsenic trioxide on the proliferation of RBMI8226 cells were time and dose-dependent,and the cell cycle was obviously blocked.Both of them could decrease the expression of bcl-2 protein and increase the expression of Bax and caspase-3 protein,Compared with single drug-treatment group,the cell survival rate and the apoptosis rate is higher in combined drug-treatment group.Conclusion Honokiol combined with Arsenic trioxide could effectively inhibit the proliferation of RBMI8226 cells,Which may be associated with the downregulation of Bcl-2 and the upregulation of Bax and caspase-3 protein expression.