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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 pyrrolidine dithiocarbamate (PDTC) combined with paclitaxel on proliferation and invasion of human breast cancer cell line MDA-MB-231 . Methods MTT and FCM were used to detect cell proliferation and cell cycle changes. The changes of NF-κB p65 mRNA were detected by RT-PCR. The protein expressions of NF-κB p65, MMP-9 and TIMP-1 were detected by Western blotting, invasion, migration and adhesion Experimental determination of cell invasion and metastasis changes. Results PDTC combined with paclitaxel significantly inhibited tumor cell growth (P <0.05) and cell cycle arrest in G1 / G0 phase, which could counteract the activation of NF-κB by paclitaxel and decreased the expression of NF-κB p65 mRNA and protein P <0.05). PDTC reduced the invasion and metastasis of MDA-MB-231 cells, and enhanced the effect with paclitaxel (P <0.01). Conclusions PDTC combined with paclitaxel can reduce the invasion and metastasis of breast cancer MDA-MB-231 cells, which may be related to the inhibition of PDTC on the expression of NF-κB.