| 16 | Tissue inhibitor of metalloproteinase-1 protects MCF-7 breast cancer cells from paclitaxel-induced apoptosis by decreasing the stability of cyclin B1显示文摘Paclitaxel(PTX) is a very effective drug in treating tumors.It disturbs microtubule dynamics and impairs the transition of cells from metaphase to anaphase in mitosis,leading to cell death by apoptosis.However,the effectiveness of PTX in cancer chemotherapy is hampered by drug resistance in some patients.Tissue inhibitor of metalloproteinase-1(TIMP-1) is well known to be capable of inhibiting apoptosis.Elevated tumor tissue TIMP-1 levels have been significantly associated with a poor response to chemotherapy.We hypothesized that TIMP-1 could reduce the sensitivity of breast cancer cells to PTX by inhibiting apoptosis.To test this hypothesis,we first examined the effects of TIMP-1 on the apoptosis induced by PTX and investigated the effects of TIMP-1 on the expression and stability of cyclin B1 that critically regulates the metaphase to anaphase transition during mitosis in MCF-7 breast cancer cells.Our data demonstrate that TIMP-1 could significantly decrease the sensitivity of MCF-7 cells to PTX-induced apoptosis,attenuate mitotic blockage in G(2) /M,and enhance the degradation of cyclin B1.To further investigate whether the inhibitory effect of TIMP-1 on PTX-induced apoptosis is mediated by lowering levels of cyclin B1,a cyclin B1-expression plasmid was transfected into clone overexpressing TIMP-1.The levels of PTX-induced apoptosis were then analyzed.The data showed that the TIMP-1-based decrease in PTX-induced apoptosis was reversed by cyclin B1.Our data indicate that TIMP-1 can protect breast cancer cells from PTX-induced apoptosis by decreasing the stability of cyclin B1. | Wang,T Lv,JH Zhang,XF Li,CJ Han,X Sun,YJ Nanjing Med Univ,Key Lab Human Funct Genom Jiangsu Prov,Nanjing 210029,Peoples R China Nanjing Med Univ,Dept Cell Biol & Med Genet,Nanjing 210029,Peoples R China Nanjing Univ,Sch Med,Nanjing 210008,Peoples R China Nanjing Med Univ,Ctr Canc,Nanjing 210029,Peoples R China | 2010 | 南京医科大学学报(自然科学版)2010，30，5： | 1 |
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