褪黑素通过内质网应激诱导骨髓瘤RPMI 8226细胞凋亡  

Melatonin Induced Apoptosis of RPMI 8226 Cells through Endoplasmic Reticulum Stress

作　　者：陈婷 李历程 张燕 马丹 王季石 李梦醒 CHEN Ting;LI Li-Cheng;ZHANG Yan;MA Dan;WANG Ji-Shi;LI Meng-Xing(Department of Hematology,Guizhou Medical University Affiliated Hospital,Guiyang 550004,Guizhou Province,China)

机构地区：[1]贵州医科大学附属医院血液内科,贵州贵阳550004

出　　处：《中国实验血液学杂志》2022年第4期1156-1161,共6页Journal of Experimental Hematology

基　　金：国家自然科学基金(81760039,81960476,81460365);贵州省科技厅计划项目(2020⁃4Y160,20191270);贵阳市科技局国基培育(GY2015⁃35,J⁃2015⁃09);贵州省卫生健康委科学技术基金项目(gzwkj2021⁃160)。

摘　　要：目的:初步探讨褪黑素(melatonin,MLT)对人多发性骨髓瘤细胞株RPMI 8226增殖、凋亡的影响及其可能的机制。方法:体外培养RPMI 8226细胞,不同浓度的MLT作用于RPMI 8226细胞,CCK⁃8法、甲基纤维素克隆实验检测MLT对细胞增殖的作用,Annexinv⁃FITC/PI、流式细胞术检测MLT对细胞凋亡的影响,Western blot检测细胞中凋亡蛋白及内质网应激相关蛋白的表达,CCK⁃8法检测MLT与硼替佐米(Bortezomib,BTZ)联合使用对RPMI 8226细胞活力的影响。结果:与对照组比较,MLT组细胞活力明显降低,呈药物剂量和时间依赖性(r=-0.9777,r=-0.9951),克隆形成数目减少,细胞凋亡增加(P<0.05),抗凋亡蛋白XIAP表达降低,凋亡蛋白Bax、Caspase3表达升高,内质网应激相关蛋白表达升高。与单独BTZ组比较,MLT与BTZ联合组RPMI 8226细胞的存活率明显降低(P<0.01)。结论:MLT可抑制骨髓瘤RPMI 8226细胞增殖,促进RPMI 8226细胞凋亡,增强BTZ对RPMI 8226细胞抗肿瘤作用,其机制可能与内质网应激有关。Objective:To investigate the effect of melatonin(MLT)on the proliferation and apoptosis of human multiple myeloma cell line RPMI 8226 and its possible mechanism.Methods:RPMI 8226 cells were cultured in vitro,and different concentrations of MLT were treated on RPMI 8226 cells.The effects of MLT on RPMI 8226 cell proliferation were detected by CCK⁃8 assay and methylcellulose cloning assay,and the effects of MLT on cell apoptosis were detected by AnnexinV⁃FITC/PI,flow cytometry.Western blot was used to determine the expression of apoptosis and endoplasmic reticulum stress⁃related proteins in each group,and CCK⁃8 assay was used to determine the effect of MLT combined with bortezemib on the viability of RPMI 8226 cells.Results:MLT inhibited the proliferation of RPMI 8226 cells in a dose⁃and time⁃dependent manner(r=-0.9777,r=-0.9951).With the increase of MLT concentration,the number of clones decreased,the apoptosis of RPMI 8226 cells increased(P<0.05),the expression of anti⁃apoptotic protein XIAP decreased,the expression of apoptotic proteins Bax and Caspase3 increased,and the expression of endoplasmic reticulum stress⁃related proteins increased.Compared with the control group,the survival of RPMI 8226 cells in the MLT and BTZ combined group significantly decreased(P<0.01).Conclusion:MLT can inhibit the proliferation of RPMI 8226 cells,promote the apoptosis of RPMI 8226 cells,and enhance the anti⁃tumor effect of BTZ on RPMI 8226 cells.The mechanism may be related to endoplasmic reticulum stress.

关 键 词：褪黑素 骨髓瘤细胞 内质网应激 凋亡 

分 类 号：R733.1[医药卫生—肿瘤]