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细胞周期蛋白依赖激酶Roscovitine诱导非小细胞肺癌A549细胞凋亡及其机制的研究 被引量:1

Cyclin Dependent Kinase Inhibitor Roscovitine-induced Apoptosis in Non-small Cell Lung Cancer A549 Cells and Its Mechanisms
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摘要 目的:探讨细胞周期蛋白依赖激酶(CDK)抑制剂Roscovitine(Ros)诱导非小细胞肺癌(NSCLC)A549细胞凋亡及其作用机制。方法:以不同浓度Ros(10μM、20μM、40μM)处理细胞24h,采用Annexin V-PI染色以流式细胞仪检测细胞凋亡,Westernblot法检测胞浆中和线粒体促凋亡蛋白Bax和Bad的表达,流式细胞仪检测线粒体膜电位(MMP)变化。结果:Ros以剂量依赖的方式诱导A549细胞凋亡,同时Bad和Bax在胞浆的含量随着Ros剂量的增加而减少,而在线粒体中却出现相反的结果,线粒体膜电位随Ros剂量的增大而降低。结论:Ros可通过促进Bax和Bad由胞浆向线粒体易位,诱导NSCLC A549细胞由线粒体途径发生凋亡。 Objective: To investigate the effect of cyclin dependent kinase inhibitor roscovitine (Ros)-induced apoptosis on non-small cell lung cancer A549 cells and its mechanisms. Methods: A549 cells were exposed to varying concentrations of Ros for 24h. Apoptosis was detected with Annexin V-PI staining by flow cytometry. The expression of pro-apoptotic protein Bax and Bad in cytoplasm and mitochondria was detected by western blot. The changes of mitochondrial membrane potential (MMP) were analyzed by flow cytometry. Results: Roscovitine could effectively induce apoptosis and this effect increased with the increasing of the drug concentration. The expression levels of Bax and Bad in the cytosol declined with Ros treatment, while increased in the mitochondria, and which was in a dose-dependent manner. Ros also caused decreasing of MMP dose-dependently. Conclusionsi Ros induced apoptosis in A549 cells in a dose-dependent way by facilitating mitochondrial translocation of Bax and Bad, thus activating mitochondrial apoptotic pathway.
出处 《现代生物医学进展》 CAS 2011年第20期3835-3837,3829,共4页 Progress in Modern Biomedicine
关键词 ROSCOVITINE 肺癌细胞 细胞凋亡 BAX BAD Roscovitine Non-small cell lung cancer Apoptosis Bax Bad
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  • 1Wesemann W, Grote C, Clement HW, et al. Functional studies on monoaminergic transmitter release in parkinsonism. Prog Neuropsychopharmacol Biol Psychiatry, 1993, 17:487-499.
  • 2Shimura H, Hattori N, Kubo S, et al. Familial parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet, 2000,25:302-305.
  • 3Beites CL, Xie H,Bowser R,et al. The septin CDCrel-1binds syntaxin and inhibits exocytosis. Nature Neurosci, 1999,2: 434-439.
  • 4Yang E, Zha J, Jockel J, et al. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death [J]. Cell, 1995, 80 (2): 285-291.
  • 5Wei MC, Zong WX, cheng EH, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfimction and death[J]. Science, 2001,292(5517): 727-730.
  • 6Mgbonyebi OP, Russo J, Russo IH. Roscovitine induces cell death and morphological changes indicative of apoptosis in MDA-MB-231 breast cancer cells[J]. Cancer Res, 1999, 59:1903-1910.
  • 7Hahntow IN, Schneller F, Oelsner M, et al. Cyclin dependent kinase inhibitor roscovitine induces ap0ptosis in chronic lymphocytic leukemia cells[J]. Leukemia, 2004, 18:747-755.
  • 8Tirado OM, Mateo-lozano S, Notario V. Roscovitine is an effective inducer of apoptosis of Ewing's sarcoma family tumor cells in vitro and in vivo[J]. Cancer Res, 2005, 65:9320-9327.
  • 9Mohapatra S, Chu B, Zhao XH, et al. Accumulation of p53 and reductions in XIAP abudance promote the apoptosis of prostate cancer cells[J]. Cancer Res, 2005, 65:7717-7723.
  • 10Wojciechowski J, Horky M, Gueorguieva M, et al. Rapid onset of nucleolar disintegration preceding cell cycle arrest in roseovitine-indueed apoptosis of human MCF-7 breast cancer[J]. Int J Cancer, 2002, 106:486-495.

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  • 1Pavletich N P. Mechanisms of cyclin-dependent kinase regulation: structures of cdks, their cyclin activators, and cip and INK4 in- hibitors [J]. J Mol Biol, 1999, 287( 5 ): 821.
  • 2Ibrahim D A, E1-Metwally A M. Design, synthesis, and tfiological evaluation of novel pyrimidine derivatives as CDK2 inhibitors [J]. Eur J Med Chem, 2010, 45(3 ):1158.
  • 3Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a chang- ing paradigm [J]. Nat Rev Cancer, 2009, 9( 3 ): 153.
  • 4Fuster J J, Fernmdez P, Gonz61ez-Navarro H, et al. Control of <'ell proliferation in atherosclerosis: insights from animal models and human studies [J]. Cardiovascular Res, 2010, 86(2 ): 254.
  • 5Arris C E, Boyle F T, Calvert A H, et al. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles [J]. J Med Chem, 2000, 43( 15 ): 2797.
  • 6Edgar B A, Orr-Weaver T L. Endoreplication cell cycles: more for less [J]. Cell, 2001, 105(3): 297.
  • 7Prehoda K E, Lim W A. How signaling proteins integrate multiple inputs: a comparison of N-WASP and Cdk2 [J]. Curr Opin Cell Bi- ol, 2002, 14(2): 149.
  • 8Elgazwy A S, Ismail N S, Elzahabi H S. A convenient synthesis and molecular modeling study of novel purine and pyrimidine deriva- tives as CDK2/cyclin A3 inhibitors[J]. Bioorg Med Chem, 2010, 18 (21): 7639.
  • 9Sharma P S, Sharma R, Tyagi R. Inhibitors of cyclin dependent ki- nases: useful targets for cancer treatment[J]. Curr Cancer Drug Tar- gets, 2008, 8( 1 ): 53.
  • 10Sallam H, Jimenez P, Song H, et al. Age-dependent pharmacoki- netics and effect of roscovitine on Cdk5 and Erk 1/2 in the rat brain [J]. Pharmacol Res, 2008, 58( 1 ): 32.

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