弗林蛋白转换酶抑制剂对乳腺癌 MCF-7细胞增殖的影响

Effect of Furin Inhibitor on Growth of Breast Cancer MCF-7 Cell

目的探讨弗林蛋白酶(Furin)抑制剂在乳腺癌细胞增殖中的作用,为深入研究乳腺癌发生、发展机制提供理论基础。方法以不同浓度Furin抑制剂处理MCF-7细胞,噻唑蓝(MTT)法检测Furin抑制剂对MCF-7细胞增殖的影响,Hochest 33342染色法检测细胞凋亡,Western blot检测细胞凋亡通路相关蛋白(Caspase-3,Caspase-8,Caspase-9)表达水平,酶联免疫吸附(ELISA)法检测Furin抑制剂对细胞超氧化物调节相关酶类活性。结果 Furin抑制剂对MCF-7细胞生长有明显抑制作用,而且抑制作用呈剂量、时间依赖性。Hochest 33342染色发现MCF-7细胞出现明显凋亡;Western blot结果显示,细胞凋亡通路相关蛋白Caspase-3,Caspase-8及Caspase-9表达显著增高。一定浓度的Furin抑制剂作用细胞48 h后,显著增高细胞内超氧化物歧化酶及过氧化氢酶活性。结论 Furin抑制剂通过调节MCF-7细胞氧化还原状态,诱导MCF-7细胞凋亡,进而抑制细胞的增殖。

Objective To investigate the role of Furin in breast cancer cell proliferation and provide a theoretical basis for in-depth study of breast cancer. Methods Different concentrations of Furin inhibitor were added in MCF-7 cell culture to test MCF-7 cell proliferation by MTT essay.Hochest 33342 staining was used to detect the morphological change of apoptosic cells.Western blot analysis was applied to measure the level of cell apoptosis associated proteins,such as Caspase-3,Caspase-8 andCaspase-9.The enzyme-linked immunosorbent assay was used for detection the CAT and SOD levels in cell culture. ResultsMCF-7 cell growth was inhibited by Furin inhibitor in a time and dose dependent manner.The results of Western blot and Hochest33342 staining indicated that MCF-7 cells were apoptosis after Furin inhibitor treatment. The level of CAT was increasedsignificantly,associated with the level of SOD. Conclusion Furin inhibitor could induce MCF cell apoptosis, thereby inhibitcell proliferation by modulating MCF-7 cell redox state.