姜黄素对K562细胞增殖的影响及其与P210^(bcr/abl)激活的Ras信号途径的关系  

Inhibition of curcumin on proliferation of K562 cells and down-regulation of P210^(bcr/abl)- initiated Ras signal pathway

作　　者：吴丽贤[1] 许建华[1] 吴国华[1] 陈元仲 

机构地区：[1]福建医科大学临床药理研究所.药理学教研室,福州350004 [2]福建省血液病研究所,福州350004

出　　处：《中国药理学通报》2003年第1期33-37,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金 (No 30 17115 8);福建省自然科学基金重点项目(NoC992 0 0 1)资助

摘　　要：目的　研究姜黄素 (Cur)对慢性粒细胞白血病 (CML)细胞株K5 62增殖的影响 ,并且探讨这种影响与P2 10 bcr/abl及其激活的Ras信号途径的关系。方法　应用MTT法检测Cur对细胞增殖的影响 ,应用Westernblot的方法检测蛋白含量的变化。结果　Cur对P2 10 bcr/abl阳性的K5 62细胞抑制作用呈量效、时效关系 ,Cur 10mg·L-1作用 48h对K5 62细胞的抑制率高达 (81 9± 1 0 ) % ;相比之下 ,已知对P2 10 bcr/abl无影响的VP 16作为抗癌药对照 ,对K5 62细胞的抑制作用明显较弱。Cur和VP 16对K5 62细胞的不同作用提示Cur对K5 62细胞作用可能有特异性 ,而这个特异的作用靶点可能就是引起CML对多种化疗药物耐药的CML特征性的P2 10 bcr/abl蛋白。Westernblot的实验结果表明Cur使K5 62细胞P2 10 bcr/abl、MEK 1和c Jun蛋白含量明显减少 ,且呈量效关系 ,相比之下 ,VP 16对K5 62细胞P2 10 bcr/abl的蛋白含量无影响而仅轻微减少MEK 1和c Jun的蛋白含量 ,提示MEK 1和c Jun蛋白含量的减少是非特异性的 ,并且 ,在P2 10 bcr/abl阳性的K5 62细胞 ,Cur除了非特异性地抑制细胞中MEK 1及c Jun的表达外 ,Cur还可能通过特异性地抑制K5 62细胞的特异性靶点P2 10 bcr/abl的表达 ,从而下调其下游的Ras信号途径中的其它信号分子。AIM To study the effects of curcumin(Cur) on proliferation of K562 cells and the relationship of the effects to Ras signal transduction pathway activated by P210 bcr/abl . METHODS MTT was used to determine the proliferative effects of drugs on tumor cells. Western blotting was used to examine the abundance of signal protein molecules expressed by tumor cells. RESULTS Exposure of K562 cells to Cur produced both dose and time dependent increase in proliferative inhibition rate. The inhibition rate of K562 cells treated by Cur 10 mg·L -1 for 48 h was as high as (81 9±1 0)%. In contrast, as anticancer drug control, VP 16, which has no influence on P210 bcr/abl , inhibited the proliferation of K562 cells only slightly. The different effects between Cur and VP 16 on K562 cells suggested that Cur can inhibit the proliferation of K562 cells specifically, and this specific target may be P210 bcr/abl , which initiates several signal pathways that is responsible for the resistance of CML cells to several chemotherapeutic agents. The abundance of P210 bcr/abl as well as c Jun and MEK 1 proteins were strongly down regulated in curcumin treating P210 bcr/abl positive K562 cells while c Jun and MEK 1 proteins were only slightly down regulated in VP 16 treating K562 cells, moreover, VP 16 had no influence on P210 bcr/abl . The results suggest that Cur can down regulate the abundance of P210 bcr/abl specifically in P210 bcr/abl positive K562 cells resulting in the down regulation of its downstream molecules, while the reduction of c Jun and MEK 1 was not specific. CONCLUSION Curcumin induced inhibition of the proliferation of K562 cells correlates with down regulation of the abundance of P210 bcr/abl , which may ultimately lead to retard ation of the Ras signal transduction pathway.

关 键 词：细胞增殖 信息途径 姜黄素 P210^bcr/abl MEK-1 C-JUN 

分 类 号：R285[医药卫生—中药学]