期刊文献+

全反式维甲酸诱导胃腺癌细胞周期阻滞的作用机制 被引量:2

Effects of All Trans Retinoic Acid on Cell Cycle Arrest of Gastric Carcinoma Cell Line and Its Mechanism
原文传递
导出
摘要 目的:研究全反式维甲酸(all trans retinoic acid,ATRA)对人胃腺癌细胞(SGC-7901)细胞周期阻滞的诱导作用并探讨其机制。方法:采用四甲基偶氮唑盐(MTT)方法检测ATRA对SGC-7901增殖的抑制;流式细胞术检测细胞周期,Westernblot方法检测不同浓度ATRA处理后的SGC-7901细胞中Akt、p-Ak(tSer473)、p-Ak(tThr308)、p-GSK-3β(Ser9)和cyclinD1的表达情况。结果:10-9~10-5mol/L的ATRA作用SGC-7901细胞48h,能显著抑制细胞增殖,其抑制率分别为10.2%±0.5%、15.3%±0.5%、17.0%±0.7%、28.4%±1.0%和36.9%±0.7%;G1期细胞比率随着ATRA浓度的增加而增加,呈明显的G1期阻滞;Westernblot检测显示ATRA对细胞中Akt蛋白的表达没有明显影响,两种p-Akt蛋白的表达显著下调,ATRA显著降低细胞中cyclinD1和p-GSK-3β的表达。结论:ATRA可能通过抑制磷酸化Akt蛋白表达而减少p-GSK-3β的表达,从而减少cyclinD1的表达量,进而诱导SGC-7901细胞发生G1期阻滞。 Objective:To investigate the effects of all trans retinoic acid(ATRA) on cell cycle arrest of human gastric carcinoma cell line(SGC-7901) and its mechanism.Methods:The effects of ATRA on the cell proliferation was detected by methyl thiazolyl tetrazolium(MTT),cell cycle was detected by flow cytometry,and the expression of Akt,p-Akt(Ser473),p-Akt(Thr308),P-GSK-3β(Ser9) and cyclin D1 were measured by Western blot.Results:SGC-7901 cells were exposed to 10-9-10-5mol/L ATRA for 48 hours,and the inhibitory rate was 10.2%±0.5%,15.3%±0.5%,17.0%±0.7%,28.4%±1.0% and 36.9%±0.7%,respectively.The proportion of SGC-7901 cells at G1 phase increased significantly with the increasing of the ATRA concentration,which showed apparent G1 phase arrest.ATRA did not influence the expression of Akt,but decreased the expression of p-Akt(Ser473) and p-Akt(Thr308);ATRA significantly decreased the expression of cyclin D1 and p-GSK-3β.Conclusion:ATRA could induce G1 phase arrest by decreasing the expression of p-Akt(Ser473) and p-Akt(Thr308),and the subsequent suppression of p-GSK-3βand cyclin D1.
出处 《现代生物医学进展》 CAS 2010年第13期2416-2418,共3页 Progress in Modern Biomedicine
基金 黑龙江省教育厅科学技术研究项目(11521182) 黑龙江省自然科学基金资助项目(D2007-79)
关键词 全反式维甲酸 胃癌 Akt CYCLIND1 GSK-3Β All trans retinoic acid Gastric cancer Akt cyclin D1 GSK-3β
  • 相关文献

参考文献13

  • 1Ferrara F. Acute promyelocytic leukemia: what are the treatment options?[J]. Expert Opin Pharmacother, 2010,11(4):587-596.
  • 2Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable[J]. Blood, 2008, 111(5):2505-2515.
  • 3Coelho SM, Vaisman M, Carvalho DP. Turnout re-differentiation effect of retinoic acid: a novel therapeutic approach for advanced thyroid cancer[J]. Curt Pharm Des, 2005,11 (19):2525-2531.
  • 4Sun SY, Lotan R. Retinoids and their receptors in cancer development and chemoprevention[J]. Crit Rev Oncol Hematol, 2002,41 (1):41 -55.
  • 5Wu Q, Chen ZM, Su WJ. Anticancer effect of retinoic acid via AP-1 activity repression is mediated by retinoic acid receptor alpha and beta in gastric cancer cells [J]. Int J Biochem Cell Biol, 2002,34 (9): 1102-1114.
  • 6Chang Q, Chen Z, You J, et al. All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma cell line[J]. J Neurooncol, 2007, 84(3):263-267.
  • 7Michl P, Downward J. Mechanisms of disease: PI3K/AKT signaling in gastrointestinal cancers[J]. Z Gastroenterol, 2005,43(10): 1133-1139.
  • 8Porta C, Figlin RA. Phosphatidylinositol-3-kinase/Akt signaling pathway and kidney cancer, and the therapeutic potential of phosphatidylinositol-3-kinase/Akt inhibitors[J]. J Urol, 2009,182(6): 2569-2577.
  • 9Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: Its functions and alterations in human cancer[J]. Apoptosis, 2004,9(6):667-676.
  • 10Steelman LS, Stadelman KM, Chappell WH, et al. Akt as a therapeutic target in cancer[J]. Expert Opin Ther Targets, 2008,12(9):1139-1165.

同被引文献16

  • 1陈玉强,吴晓安,洪节约,崔殿龙,万幼峰.FAM及FAM辅加ATRA方案对胃癌术后患者疗效对比观察[J].实用癌症杂志,2005,20(2):166-168. 被引量:2
  • 2卢航青,郑杰.全反式维甲酸和1α,25二羟维生素D_3对肝癌细胞HepG2生长的协同抑制作用[J].癌症,2006,25(12):1470-1476. 被引量:12
  • 3Huang M E,Ye Y C,Chen S R.et al.Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia[J].Blood,1988,72(2):567-72.
  • 4Engelman J A,Zhang X L,Galbiati F,et al.Chromosomal localization,genomic organization,and developmental expression of the murine caveolin gene family (Cav-1,-2,and-3) Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/7q31)[J].FEBS Lett,1998,429(3):330-6.
  • 5Coelho S M,Vaisman M,Carvalho D P.Tumour re-differentiation effect of retinoic acid:a novel therapeutic approach for advanced thyroid cancer[J].Curr Pharm Des,2005,11(19):2525-31.
  • 6Capozza F,Williams T M,Schubert W,et al.Absence of caveolin-1 sensitizes mouse skin to carcinogen induced epidermal hyperplasia and tumor formation[J].Am J Rathol,2003,162(6):2029-39.
  • 7Allen J A,Yu J Z,Dave R H,et al.Caveolin-1 and lipid microdomains regulate Gs trafficking and attenuate Gs/adenylyl cyclase signaling[J].Mol Pharmacol,2009,76(5):1082-93.
  • 8Wang X Q,Yan Q,Sun P,et al.Suppression of epidermal growth factor receptor signaling by protein kinase C-α activation requires CD82,caveolin-1,and ganglioside[J].Cancer Res,2007,67(20):9986-95.
  • 9Place A T,Chen Z L,Bakhshi F R,et al.Cooperative role of Caveolin-1 and C-Terminal Src kinase binding protein in C-terminal Src kinase-mediated negative regulation of c-Src[J].Mol Pharmacol,2011,80(4):665-72.
  • 10Cerezo A,Guadamillas M C,Goetz J G,et al.The absence of caveolin-1 increases proliferation and anchorage-independent growth by a Rac-Dependent,Erk-Independent mechanism[J].Mol Cell Biol,2009,29(18):5046-59.

引证文献2

二级引证文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部