姜黄素增加白血病细胞KG1a对阿糖胞苷敏感性的研究  

Molecular mechanism of curcumin on the promotion of cytarabine sensitivity in human acute myeloid leukemia cells KG1a

作　　者：白天鸽 马翠[1] 李瑶瑶 魏虹[1] BAI Tian-ge;MA Cui;LI Yao-yao;WEI Hong(Department of Histology and Embryology,School of Medicine^Shihezi University,Shihezi 832002,Xinjiang Uyghur Autonomous Region,China)

机构地区：[1]石河子大学医学院组织胚胎学教研室,新疆维吾尔自治区石河子832002

出　　处：《中国临床药理学杂志》2021年第23期3262-3265,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81460024)。

摘　　要：目的探讨姜黄素促进阿糖胞苷对人急性髓系白血病KG1a细胞株增殖抑制和凋亡的分子机制。方法将细胞分为9组:空白对照组、4个不同浓度(20,40,60,80μmol·L^(-1))姜黄素组(分别命名为姜黄素-1,-2,-3,-4组)和4个不同浓度(20,100,500,2500 nmol·L^(-1))阿糖胞苷组(分别命名为阿糖胞苷-1,-2,-3,-4组),测定各组细胞的增殖抑制率,筛选最佳浓度,以半数致死率的姜黄素浓度(40μmol·L^(-1),姜黄素-2组)联合上述4个不同浓度阿糖胞苷组(命名为联合-1,-2,-3,-4组),处理24和48 h,测定各组细胞凋亡率,筛选出最佳浓度的联合组(阿糖胞苷-3组+姜黄素-2组),测定凋亡相关蛋白半胱氨酸蛋白酶-3(Caspase3)、Cleved caspase-3、B淋巴细胞瘤-2(Bcl-2)和细胞色素C(CytC)释放的表达水平(灰度值)。结果处理24 h,空白对照组、阿糖胞苷-3组、姜黄素-2组和最佳联合组的细胞增殖抑制率分别为(1.22±0.29)%,(33.80±1.00)%,(21.17±2.27)%和(45.26±1.13)%;这4组的凋亡率分别为(0.18±0.23)%,(4.96±1.42)%,(8.10±1.32)%和(13.45±1.03)%;这4组的Bcl-2蛋白表达水平分别为2.01±0.56,0.71±0.24,0.63±0.31和0.22±0.19;这4组的Cleved caspase-3/Caspase-3的比值分别为0.86±0.22,1.14±0.34,1.23±0.29和1.52±0.47;这4组的线粒体CytC与内参蛋白的比值分别为1.30±0.21,1.53±0.37,1.92±0.24和2.17±0.29。阿糖胞苷组和姜黄素组的上述指标与空白对照组比较,或联合组的上述指标与阿糖胞苷组和姜黄素组比较,差异均有统计学意义(均P<0.05)。48 h结果同上。结论姜黄素可以增加白血病细胞对阿糖胞苷的敏感性,可通过调节Caspase3的活化、调节Bcl-2蛋白及CytC的表达诱导白血病细胞KG1a产生凋亡。Objective To explore the molecular mechanism of curcumin in promoting the proliferation and apoptosis of the chemotherapeutic drug cytosine arabinoside on the human acute myeloid leukemia KG1a cel line.Methods The cells were divided into 9 groups:Blank contro group,curcumin groups with different concentrations(20,40,60,80μmol·L^(-1);named as curcumin-1,-2,-3,-4 groups)and cytarabine groups with different concentrations(20,100,500,2500nmol·L^(-1);named as cytarabine-1,-2,-3,-4 groups),the bes selection concentration which is the half-lethal curcumin concentration40μmol·L^(-1),curcumin-2 group)combined with the above 4different concentrations of cytarabine group(named combined-1,-2,-3,-4 groups),treated for 24,48 h;and screened the combination group with the best concentration(cytarabine-3 group+curcumin-2 group).The cell proliferation inhibition rate,apoptosis rate and expression level of apoptosis-related proteins Caspase-3,Cleved caspase-3,B-cell lymphoma-2(Bcl-2)and cytochrome C(CytC)release were measured.Results After treated for 24 h,the cell proliferation inhibition rates of blank control group,cytarabine group,curcumin group and the best combination group were(1.22±0.29)%,(33.80±1.00)%,(21.17±2.27)%,(45.26±1.13)%,respectively;the apoptosis rate in the 4 groups were(0.18±0.23)%,(4.96±1.42)%,(8.10±1.32)%,(13.45±1.03)%,respectively;the expression levels of Bcl-2 protein in the 4 groups were 2.01±0.56,0.71±0.24,0.63±0.31,0.22±0.19,respectively;the ratio of Cleved caspase-3/Caspase-3 in the 4 groups were 0.86±0.22,1.14±0.34,1.23±0.29 and 1.52±0.47,respectively;the ratio of CytC/internal reference protein in the 4 groups were1.30±0.21,1.53±0.37,1.92±0.24,2.17±0.29,respectively.Compared between cytarabine group,curcumin group and blank control group,or between combination group and cytarabine group,curcumin group,the difference of the above indicators were statistically significant(all P<0.05);and the 48 h results were the same as 24 h.Conclusion Curcumin can increase the sensitivity of le

关 键 词：姜黄素 阿糖胞苷 急性髓系白血病 增殖 凋亡 

分 类 号：R97[医药卫生—药品]