PDTC联合紫杉醇降低MDA-MB-231细胞增殖侵袭能力

Combination of pyrrolidine dithiocarbamate and paclitaxel suppresses proliferation and invasion of MDA-MB-231 cells

目的探讨核因子-κB(NF-κB)抑制剂——吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)联合紫杉醇(Paclitaxel)对人乳腺癌MDA-MB-231细胞增殖侵袭能力的影响。方法MTT及FCM法测定细胞增殖和周期变化,RT-PCR检测细胞NF-κB p65 mRNA的变化,Western blot检测细胞NF-κB p65、MMP-9及TIMP-1蛋白表达变化,侵袭、迁移和黏附实验测定细胞侵袭转移能力的改变。结果PDTC联合紫杉醇能明显抑制肿瘤细胞生长(P<0.05),细胞周期阻滞在G1/G0期,并可抵消紫杉醇对NF-κB的激活,使NF-κB p65 mRNA及蛋白的表达均降低(P<0.05)。PDTC降低MDA-MB-231细胞的侵袭转移能力,与紫杉醇联合应用后作用增强(P<0.01)。结论PDTC联合紫杉醇能降低乳腺癌MDA-MB-231细胞的侵袭转移能力,其机制可能与PDTC抑制NF-κB的表达相关。

Objective To investigate the effect of the nuclear factor-κB （NF-κB） inhibitor, pyrrolidine dithiocarbamate （PDTC） and paclitaxel on the proliferation and invasion of human breast cancer cell line MDA-MB-231. Methods The MDA-MB-231 cells were treated with PDTC （100 μmol/L） or paclitaxel （ 1 μmol/L） , or combined treatment. The effect of proliferation was analyzed by MTT assay. The cell cycle was evaluated by flow cytometry. RT-PCR was used to detect the expression of NF-κB p65 mRNA. Western blotting were used to determing the expression of NF-κB p65, MMP-9 and TIMP-1 in MDA-MB-231 cells after treatment. The invasion ability of MDA-MB-231 cells was tested ty the invasion, migration and cell adhesion assay. Results The cell growth was significantly slowed down and the cell cycle was arrested at G0/Gl phase after combined treatment. The expression of NF-κB p65 and MMP-9 was downregulated （ P 〈 0.05 ） compared with paclitaxel treatment group, and the invasion ability of MDA-MB-231 cells was decreased after combined treatment （P 〈 0. 01 ）. Conclusion PDTC combined with paclitaxel effectively inhibits cell proliferation, induces cell cycle arrest, and decreases cell invasion ability of human breast cancer MDA-MB-231 cells. Its mechanism may be associated with PDTC inhibiting the NF-κB-related gene expression.