姜黄素抑制RPMI8226细胞增殖时丝裂原活化蛋白激酶及基质金属蛋白酶的表达  

Inhibitory effect of curcumin on the expressions of MAPKs and MMPs in RPMI8226 cells during their proliferation

作　　者：朱国华[1] 张琦[1] 戴海萍[2] 沈群[3] 

机构地区：[1]南京中医药大学第一临床医学院,南京医学博士210023 [2]苏州大学第一附属医院血液科,苏州215006 [3]南京中医药大学第一附属医院血液科,南京210029

出　　处：《医学研究生学报》2014年第10期1016-1019,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81274139);江苏省高校自然科学研究基金(14KJB320010);江苏省普通高校研究生科研创新计划项目(CXLX12_0583);南京中医药大学青年自然科学基金(13XZR13)

摘　　要：目的姜黄素(Curcumin,Cur)对多种肿瘤细胞均具有明确的抑制增殖、诱导凋亡与部分分化、抑制迁移等方面作用。文中研究Cur体外抑制人多发性骨髓瘤细胞RPMI8226增殖时丝裂原活化蛋白激酶(mitogen actived protein kinase,MAPKs)及基质金属蛋白酶(matrix metalloproteinases,MMPs)家族成员的表达,探讨Cur的抗肿瘤分子机制。方法以不同浓度Cur作用RPMI8226细胞不同时间,MTT检测细胞增殖抑制率,流式细胞术检测细胞周期变化,Western blot检测MAPKs家族成员的表达,明胶酶谱法检测细胞培养上清中MMPs的活性。结果 Cur呈时间-剂量依赖性抑制RPMI8226细胞增殖,使细胞阻滞于G2/M期[(12.72±0.68)%vs(4.79±0.15)%]。以6.25μmol/L、12.50μmol/L及25.00μmol/L Cur分别处理RPMI8226细胞,细胞内JNK和p-JNK的表达均呈药物浓度依赖性上升(P<0.01),而ERK1/2及P38 MAPK的表达与阴性对照组相比无明显改变(P>0.05)。另各Cur处理组的细胞培养上清中MMP-2及MMP-9的活性,随着Cur药物浓度的上升而逐渐下降(P<0.01)。结论一定浓度的Cur不仅可能激活MAPKs家族中的JNK信号通路,体外诱导RPMI8226细胞的凋亡,且还可能通过抑制MMPs的活性,影响RPMI8226细胞的浸润与转移。Objective curcumin can suppress the proliferation , induce apoptosis and partial differentiation , and inhibit the migration of many kinds of tumor cells .The aim of this study was to investigate the expressions of mitogen-activated protein kinase （MAPKs） and matrix metalloproteinases （MMPs） when the proliferation of human multiple myeloma RPMI8226 cells was inhibited by curcumin in vitro, and to reveal the antitumor molecular mechanism of curcumin . Methods RPMI8226 cells were treated with various concentrations of curcumin for different periods of times .The inhibitory rate of curcumin on cell proliferation was detected by MTT assay , the cell cycle analyzed by flow cytometry , the protein levels of MAPKs measured by Western blot , and the activity of MMPs analyzed by Gelatin zymography . Results Curcumin inhibited the proliferation of RPMI 8226 cells in a time-and dose-dependent manner , and the cell cycle was arrested in the G 2/M phase （[12.72 ±0.68]%vs [4.79 ±0.15]%）.The expressions of JNK and p-JNK showed a con-centration-dependent increase in the RPMI8226 cells treated with curcumin at 6.25, 12.50, and 25.00 μmol/L, respectively （P0.05）.In addition, the activities of MMP-2 and MMP-9 were decreased in a dose-depend-ent manner in the supernatant of RPMI8226 cells （ P 〈0.01）. Conclusion A certain concentration of curcumin could not only acti-vate the JNK signalling pathway of the MAPKs family and induce the apoptosis of RPMI8226 cells, but also inhibit the activity of MMPs and influence the invasion and metastasis of RPMI 8226 cells.

关 键 词：姜黄素 RPMI8226细胞 丝裂原活化蛋白激酶家族 基质金属蛋白酶家族 

分 类 号：R979.1[医药卫生—药品]