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

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。
ABSTRACT: 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 30μmol/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, 10μmol/L curcumin or 20μmol/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-κB 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