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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。
To investigate the effects of pyrrolidine dithiocarbamate (PDTC) combined with paclitaxel on the expression of matrix metalloproteinase-9 (MMP-9) in human breast cancer cell line MCF-7 Effect of Inhibitor TIMP-1 Expression and Proliferation Invasion. MTT and FCM were used to detect cell proliferation and cell cycle changes; Western blot was used to detect the expression of NF-κB p65, MMP-9 and TIMP-1; RT-PCR was used to detect the expression of NF-κB p65 mRNA; invasion, migration and adhesion The changes of cell invasion and metastasis were tested by experiments. The results showed that PDTC combined with paclitaxel significantly inhibited cell growth and blocked the cell cycle in G0 / G1 phase, which could counteract the activation of NF-κB and the expression of NF-κB p65 mRNA and MMP-9 protein (P <0.05), and had no significant effect on the expression of TIMP-1 (P> 0.05). PDTC decreased the invasion and metastasis of MCF-7 cells, and the combination group was the most obvious (P <0.001). PDTC combined with paclitaxel can reduce the invasion and metastasis of breast cancer MCF-7 cells, the mechanism may be related to PDTC inhibition of NF-κB related gene expression.