姜黄素对人子宫内膜癌细胞HEC-1-B侵袭转移的影响  

Effects of curcumin on invasion and metastasis of endometrial carcinoma HEC-1-B cells

作　　者：陈茜[1] 陈丽娟[1] 党媛媛[1] 李牧[1] 吴晓玲[1] 

机构地区：[1]西安交通大学第二附属医院妇产科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2016年第1期134-138,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省科技攻关计划项目(No.2014k11-01-01-18)~~

摘　　要：目的研究姜黄素对人子宫内膜癌细胞HEC-1-B侵袭转移的影响及其可能的机制。方法不同浓度(0、10、20、30μmol/L)的姜黄素处理HEC-1-B细胞后,MTT法检测其对HEC-1-B细胞的生长抑制作用;体外Transwell小室实验检测姜黄素和/(或)PDTC对HEC-1-B细胞迁移和侵袭能力的影响;Western blot检测姜黄素对MMP-2、MMP-9表达、活性以及p65、p50蛋白水平的影响。结果体外实验结果显示,姜黄素明显抑制子宫内膜癌细胞的生长、迁移及侵袭,且其作用呈时间-剂量依赖关系,其差异具有统计学意义(P<0.001)。此外,姜黄素处理HEC-1-B细胞24h后,细胞中MMP-2、MMP-9的表达、蛋白酶活性及P65、P50水平均明显减弱。单独使用姜黄素、PDTC组均可抑制其侵袭力,两者联合用药后对癌细胞侵袭能力的抑制效应较单独使用更明显,且明显下调MMP-2、MMP-9的表达,从而进一步拮抗HEC-1-B细胞的粘附和侵袭。结论姜黄素通过抑制上游核转录因子κB(NF-κB)活性而下调MMP-2和MMP-9的表达,进而抑制人子宫内膜癌HEC-1-B细胞的侵袭和转移。因此,姜黄素是一种潜在的子宫内膜癌治疗剂。Objective To investigate the effects and possible mechanisms of curcumin on invasion and metastasis in endometrial carcinoma HEC-1-B cells. Methods HEC-1-B cells were cultured in vitro and treated with 0, 10, 20 and 30 μmol/L of curcumin. MTT assay was performed to examine cell growth; then cell invasion assay using Transwell chamber was used to evaluate the effects of curcumin/PDTC on invasion of HEC-1-B cells. The expression and activity of matrix metalloproteinases MMP-2, MMP-9 as well as the protein levels of P65 and P50 were analyzed by Western blot. Results Compared with control group, curcumin could significantly inhibit the invasion and migration abilities of HEC-1-B cells in vitro in concentration and time-dependent manners. In addition, mechanism and functional analysis revealed that the administration of curcumin decreased the expression and activity of the extracellular matrix （ECM） factors MMP-2 and MMP-9, and the protein levels of P65 and P50, which was attributed to the suppression of anti-invasion effect produced by curcumin. Furthermore, 10 μmol/L curcumin or 20 μmol/L PDTC alone could produce similary inhibitory effect on the invasion of HEC-1-B cells. Combination of curcumin and PDTC could significantly enhance the suppressive effect, which was associated with downregulation of MMP-2/MMP-9. Conclusion These findings suggest a potential mechanism by which curcumin blocks NF-kB activity to downregulate the expression of MMP-2/MMP-9 and then inhibit the invasion and metastasis of endometrial cancer cells, suggesting that curcumin is a potent therapeutic agent for endometrial carcinoma.

关 键 词：姜黄素 子宫内膜癌 侵袭 MMPS 核转录因子ΚB 

分 类 号：R737.33[医药卫生—肿瘤]