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Mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in human breast cancer MCF-7 drug-resistant cells
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- Author:
- No author available
- Journal Title:
- ACTA PHARMACEUTICA SINICA
- Issue:
- 10
- DOI:
- 10.3321/j.issn:0513-4870.2008.10.005
- Key Word:
- SIRTI去乙酰化酶抑制剂;多药耐药性;细胞凋亡;人乳腺癌MCF-7细胞
Abstract： 研究SIRT1去乙酰化酶抑制剂引起人乳腺癌MCF-7耐多柔比星(doxorubicin,DOX)细胞及其敏感细胞凋亡的机制.MTT法检测细胞生长抑制作用;Western blotting方法检测蛋白表达;DNA特异染料Hoechst 33342染色检测染色质凝集;Annexin V检测细胞凋亡;流式细胞仪测定细胞周期分布.结果表明.SIRT1去乙酰化酶抑制剂烟酰胺(nicotinamide,NAM)和Sixtinol对人乳腺癌细胞MCF-7敏感和耐药细胞表现出相同的生长抑制作用,但没有增强DOX活性的作用.NAM使MCF-7和MCF-7/DOX细胞阻滞在(G<,2/M期.50 mmol·L-1NAM作用MCF-7细胞后,激活caspase凋亡通路,出现PARP、caspase-6、-7、-9切割片段,并且染色质发生凝集和Annexin V阳性细胞.而在MCF-7/DOX耐药细胞中,NAM作用24 h后,才开始出现PARP、caspase-6、-7切割片段,48 h后明显增加,可以检测到较多的细胞出现染色质凝集和Annexin V阳性细胞.SIRT1去乙酰化酶抑制剂对人乳腺癌MCF-7耐药细胞和敏感细胞均有相似的抑制作用,无交叉耐药性.其作用通过激活caspase凋亡通路实现.
- [1]刘艾林,龙娟,王楠,等.抗肿瘤药物新靶点：组蛋白去乙酰酶的研究进展[J].2005,(7).
- [2]Guarente L,Bordone L.Calorie restriction, SIRT1 and metabolism: understanding longevity.[J].2005,6(4).
- [3]Assam El-Osta,Phillip Kantharidis,John R. Zalcberg,etc.Precipitous Release of Methyl-CpG Binding Protein 2 and Histone Deacetylase 1 from the Methylated Human Multidrug Resistance Gene (MDR1) on Activation[J].2002,22(6).
- [4]J, Luo,A Y, Nikolaev,S, Imai,etc.Negative control of p53 by Sir2alpha promotes cell survival under stress.[J].2001,107(2).
- [5]Legrand O,Majdak P,Perrot JY,etc.Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1.[J].2004,18(7).
- [6]Pasupuleti R,Huber LJ,Solomon JM,etc.Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage[J].2006,26(1).
- [7]Marchion D,Munster P.Development of histone deacetylase inhibitors for cancer treatment.[J].2007,7(4).
- [8]Ohsawa S,Miura M.Caspase-mediated changes in Sir2 alpha during apoptosis[J].2006,580(25).
- [9]Tainton KM,Kofler R,Sutton VR,etc.The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species.[J].2001,98(19).
- [10]Jain V,Varshney R,Dwarakanath B.Radiosensitization by 6-aminonicotinamide and 2-deoxy-D-glucose in human cancer cells.[J].2005,81(5).
- [11]Amouzegh P,Napper AD,Yau WT,etc.Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1[J].2005,48(25).
- [12]Linda Tillmar,Johan Saldeen,Ella Karlsson,etc.Nicotinamide- and caspase-mediated inhibition of poly(ADP-ribose) polymerase are associated with p53-independent cell cycle (G2) arrest and apoptosis[J].2003,243(1).