Yang Chunrong, Zhang Hui, Huang Wei, Lin Qiong, Wei Huijie
Chongqing Research Centre of Molecular Medicine and Cancer, Chongqing Medical University, Chongqing 400016, China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010 Oct;27(5):1105-9.
This investigation was made with special reference to the effect of the combined use of nuclear factor-kappaB (NF-kappaB) 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-kappaB p65, MMP-9 and TIMP-1 expression in MCF-7 cells after treatment. RT-PCR was used to detect NF-kappaB 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-kappaB 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-kappaB-related gene expression.
本研究特别关注核因子-κB（NF-κB）抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）与紫杉醇联合使用对基质金属蛋白酶（MMP-9）及其抑制剂金属蛋白酶组织抑制因子-1（TIMP-1）表达的影响，以及对人乳腺癌细胞系MCF-7增殖和侵袭的影响。用PDTC和紫杉醇处理MCF-7细胞。通过MTT法评估对增殖的影响。通过流式细胞术分析细胞周期。采用蛋白质免疫印迹法检测处理后MCF-7细胞中NF-κB p65、MMP-9和TIMP-1表达的变化。采用逆转录聚合酶链反应（RT-PCR）检测NF-κB p65 mRNA表达。通过侵袭、迁移和细胞黏附试验检测MCF-7细胞的侵袭能力。联合处理后细胞生长明显减慢，细胞周期停滞于G0/G1期。联合处理后NF-κB p65和MMP-9的表达下调，MCF-7细胞的侵袭能力降低。总之，PDTC与紫杉醇联合使用可有效抑制乳腺癌MCF-7细胞的增殖，诱导细胞周期停滞，并降低细胞侵袭能力。其机制可能与PDTC对NF-κB相关基因表达的抑制作用有关。
