Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210^(bcr/abl)-initiated Ras signal transduction pathway  

姜黄素对K562细胞增殖的抑制作用与其下调p210^(bcr/abl)激活的Ras信号途径有关(英文)

作　　者：吴丽贤[1] 许建华[1] 吴国华[1] 陈元仲 

机构地区：[1]福建医科大学药理教研室 [2]福建省血液病研究所

出　　处：《Acta Pharmacologica Sinica》2003年第11期93-98,113-114,共8页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (№ 30171158 ), Ministry of Education Key Project(№ 00187), and National Key Teacher Project (00A002).

摘　　要：AIM: To investigate the effects of curcumin（Cur） on proliferation of K562 cells and the relationship between these effects and Ras signal transduction pathway activated by p210^bcr/abl. METHODS: K562 cell line was used as a p210^bcr/abl-positive cell system and HL-60 cell line as a p210^bcr/abl-negative control; etoposide（VP-16）, which has no influence on p210^bcr/abl and has resistance to K562 cells^[1], was used as an anticancer drug control to compare with curcumin. MTT was used to determine the proliferative effects of drugs on K562 and HL-60 cells. Western blot and flow cytometry were used to examine the abundance of signal protein molecules expressed in tumor cells. RESULTS: An exposure of K562 cells or HL-60 cells to Cur produced both concentration-and time-dependent increase in the anti-proliferative rate. Moreover, both cell lines had the same sensitivity to Cur（P】0.05）. In contrast, HL-60 cells had more sensitivity to VP-16 than K562 cells in anti-proliferative effect（P【0.01）. The abundance of p210^bcr/abl as well as MEK-1 and c-JUN proteins were strongly down-regulated in curcumin-treated p210^bcr/abl-positive K562 cells while c-JUN and MEK-1 proteins were only slightly down-regulated in p210^bcr/abl-negative HL-60 cells. CONCLUSION: Curcumin inhibited the proliferation of K562 cells and the inhibitory effect was correlated with down-regulation of the abundance of p210^bcr/abl, which may ultimately lead to retard the Ras signal transduction pathway. Curcumin might be worthy of being evaluated as a potential chemotherapeutic agent to CML.目的:研究姜黄素(Cur)对慢性粒细胞白血病(CML)细胞株K562增殖的影响,并且探讨这种影响与p210^(ber/abl)及其激活的Ras信号途径的关系。方法:以K562细胞为p210^(ber/abl)阳性表达细胞模型,以HL-60细胞为P210^(ber/abl)阴性表达细胞模型,以对p210^(ber/abl)无影响,并已知K562细胞对其有一定耐药性的足叶乙甙(Etoposide,VP-16)为抗癌药的对照,应用MTT法检测Cur对细胞增殖及凋亡的影响,应用Western blot及FCM方法检测蛋白含量的变化。结果:Cur对K562细胞及HL-60细胞增殖的抑制作用呈浓度和时间依赖性,并且Cur对二者的作用无差别(P>0.05);相比之下,VP-16对HL-60细胞更敏感,对K562细胞较耐药(P<0.01),Cur使K562细胞p210^(ber/abl)、MEK-1和c-JUN蛋白含量显著减少,且呈量 效关系:而同样处理的HL-60细胞的MEK-1及c-JUN的含量减少不及K562细胞明显。结论:Cur抑制K562细胞增殖的作用与Cur下调p210^(ber/abl)含量从而阻断其激活的Ras信号途径有关,从新的角度证明了姜黄素具有治疗CML的潜在价值。

关 键 词：CURCUMIN K562 cells signal transduction Bcr-Abl fusion proteins 

分 类 号：R733.7[医药卫生—肿瘤]