姜黄素联合沙利度胺抑制KG-1细胞增殖及相关作用机制研究  

Curcumin Combined with Thalidomide Inhibits Proliferation of KG-1 Cells and Its Related Mechanisms

作　　者：刘娟 黄晔 刘忠[1] LIU Juan;HUANG Ye;LIU Zhong(Department of Pharmacy,Wuhan Fourth Hospital,Wuhan 430033,Hubei Province,China)

机构地区：[1]武汉市第四医院药学部,湖北武汉430033

出　　处：《中国实验血液学杂志》2024年第2期422-427,共6页Journal of Experimental Hematology

基　　金：武汉市医学科研项目(WX21B11)。

摘　　要：目的:探讨姜黄素联合沙利度胺对急性髓系白血病KG-1细胞增殖、凋亡的影响及与抗凋亡蛋白(Bcl-xL)、信号转导和转录激活因子3(STAT3)的关系。方法:MTT法检测KG-1细胞增殖,筛选姜黄素、沙利度胺的最佳联合浓度;分别采用MTT法、流式细胞术分析姜黄素、沙利度胺单药及两药联用对KG-1细胞增殖、凋亡的影响;实时定量PCR检测单药组、两药联用组、对照组(未处理细胞)的STAT3、Bcl-xL mRNA表达水平。结果:姜黄素和沙利度胺在20-100μmol/L范围内对KG-1细胞增殖的抑制作用均呈浓度依赖性(r=0.657,r=0.681)。姜黄素在作用48h的IC50值为(42.07±0.50)μmol/L,沙利度胺为(57.01±2.39)μmol/L。姜黄素(40μmol/L)+沙利度胺(60μmol/L)两药联用的细胞增殖抑制率为(86.67±1.53)%,明显高于单用姜黄素的(51.67±1.15)%和单用沙利度胺的(55.33±1.53)%(均P<0.05)。姜黄素、沙利度胺单药及两药联用作用48h,KG-1细胞凋亡率分别为(18.67±2.08)%、(21.33±2.52)%和(46.67±1.53)%,明显高于对照组的(0.72±0.03)%(均P<0.05);两药联用组KG-1细胞凋亡率亦明显高于两药单药组(均P<0.05)。与对照组比较,姜黄素、沙利度胺单药组及两药联用组STAT3、Bcl-xL mRNA表达均显著下降(均P<0.05);与姜黄素、沙利度胺单药组比较,两药联用组STAT3、Bcl-xL mRNA表达亦显著下降(均P<0.05)。结论:姜黄素联合沙利度胺可协同下调STAT3与Bcl-xL表达,抑制KG-1细胞增殖,诱导KG-1细胞凋亡。Objective:To investigate the effects of curcumin combined with thalidomide on the proliferation and apoptosis of acute myeloid leukemia KG-1 cells,and its correlation with B-cell lymphoma-xL(Bcl-xL),signal transducer and activator of transcription 3(STAT3).Methods:MTT assay was used to detect the proliferation of KG-1 cells and screen the optimal combined concentration of curcumin and thalidomide.The effects of curcumin,thalidomide and their combination on the proliferation and apoptosis of KG-1 cells were analyzed by MTT method and flow cytometry,respectively.The mRNA expression levels of STAT3 and Bcl-xL in single-drug group,two-drug combination group and control group(untreated cells)were detected by real-time quantitative PCR.Results:Both curcumin and thalidomide inhibited the proliferation of KG-1 cells in a concentration-dependent manner in the range of 20-100μmol/L(r=0.657,r=0.681).The IC50 value of curcumin and thalidomide at 48 h was(42.07±0.50)μmol/L and(57.01±2.39)μmol/L,respectively.The cell proliferation inhibition rate of curcumin(40μmol/L)+thalidomide(60μmol/L)was(86.67±1.53)%,which was significantly higher than(51.67±1.15)%of curcumin(40μmol/L)and(55.33±1.53)%of thalidomide(60μmol/L)(both P<0.05).Treated with curcumin and thalidomide alone or in combination,the apoptosis rate of KT-1 cells was(18.67±2.08)%,(21.33±2.52)%,and(46.67±1.53)%,respectively,which was significantly higher than(0.72±0.03)%of control group(all P<0.05).The cell apoptosis rate of two-drug combination group was significantly higher than that of single-drug group(both P<0.05).Compared with the control group,the mRNA expressions of STAT3 and Bcl-xL in single-drug group,two-drug combination group were significantly decreased(both P<0.05).Compared with single-drug group,the mRNA expressions of STAT3 and Bcl-xL in two-drug combination group were also significantly decreased(both P<0.05).Conclusion:Curcumin combined with thalidomide can synergistically down-regulate the expression of STAT3 and Bcl-xL,inhibit the proli

关 键 词：急性髓系白血病 姜黄素 沙利度胺 抗凋亡蛋白 信号转导和转录激活因子3 

分 类 号：R733.71[医药卫生—肿瘤]