【摘要】 研究核因子-κB(NF-κB)抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)联合紫杉醇(Paclitaxel)对人乳腺癌MCF-7细胞的基质金属蛋白酶-9(MMP-9)及其抑制剂TIMP-1的表达和增殖侵袭能力的影响。MTT及FCM法检测细胞增殖和周期的改变;Western blot法检测细胞的NF-κB p65、MMP-9及TIMP-1蛋白表达;RT-PCR检测NF-κB p65 mRNA的表达;侵袭、迁移和黏附实验检测细胞侵袭转移能力的改变。结果表明,PDTC联合紫杉醇能明显抑制细胞生长,使细胞周期阻滞在G0/G1期,并可抵消后者对NF-κB的激活,使NF-κB p65 mRNA及其与MMP-9蛋白的表达降低(P<0.05),对TIMP-1表达没有明显影响(P>0.05);PDTC降低MCF-7细胞的侵袭转移能力,联合用药组最明显(P<0.001)。表明PDTC与紫杉醇联合应用能降低乳腺癌MCF-7细胞的侵袭转移能力,其机制可能与PDTC抑制NF-κB相关基因表达相关。更多还原

【Abstract】 This investigation was made with special reference to the effect of the combined use of nuclear factor-κB(NF-κB) inhibitor Pyrrolidine dithiocarbamate(PDTC) and Paclitaxel on the expression of Matrix metalloproteinases(MMP-9) and its inhibitor TIMP-1,and on the proliferation and invasion of human breast cancer cell line MCF-7.The MCF-7 cells were treated with PDTC and Paclitaxel.The effect on proliferation was evaluated by MTT assay.The cell cycle was analyzed by flow cytometry.Western blot was used to determine the change of NF-κB p65,MMP-9 and TIMP-1 expression in MCF-7 cells after treatment.RT-PCR was used to detect NF-κB p65 mRNA expression.The invasion ability of MCF-7 cells was tested by the invasion,migration and cell adhesion assay.The cell growth was significantly slowed down and the cell cycle was arrested at G0/G1 phase after the combined treatment.The expression of NF-κB p65 and MMP-9 was down-regulated and the invasion ability of MCF-7 cells was decreased after the combined treatment.In conclusion,PDTC combined with paclitaxel effectively inhibited cell proliferation,induced cell cycle arrest,and decreased cell invasion ability of breast cancer MCF-7 cells.The mechanism may be associated with the inhibiting effect of PDTC on the NF-κB-related gene expression.更多还原