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雷帕霉素、RAD001抑制胃癌细胞株MKN-28、MKN-45细胞生长的实验研究 被引量:2

An experimental study of the inhibitory effect of rapamycin and RAD001 on the growth of gastric carcinoma cell lines MKN-28 and MKN-45
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摘要 目的探讨雷帕霉素(rapamycin)、RAD001(everolimus)对胃癌细胞株MKN-28、MKN-45细胞生长的影响,并对其机制进行初步探讨。方法体外培养人胃癌MKN-28、MKN-45细胞,给予雷帕霉素、RAD001干预后通过细胞计数、流式细胞术检测肿瘤细胞生长、细胞周期分布情况。结果雷帕霉素、RAD001均可抑制MKN-28、MKN-45细胞生长,抑制作用具有时间依赖性,雷帕霉素作用于MKN-28、MKN-45两种细胞株72 h抑制率分别为23.40%、36.26%;RAD001作用于MKN-28、MKN-45两种细胞株72 h抑制率分别为25.12%、40.11%。72 h时RAD001组与阴性对照组、DMSO对照组相比,MKN-28、MKN-45细胞计数差异有显著性(P<0.05)。RAD001作用24 h后MKN-28、MKN-45细胞周期发生改变,停滞在G0-G1期细胞比例增加。RAD001组与阴性对照组、DMSO对照组相比,MKN-45细胞周期差异有显著性(P<0.05),MKN-28细胞周期差异无显著性(P>0.05)。结论两种药物相比较,RAD001相对敏感;两株细胞相比较,MKN-45相对敏感。RAD001通过调节细胞周期进而抑制胃癌细胞的增殖。 Objective To investigate the effect of rapamycin and RAD001 on the growth of gastric carcinoma cell lines MKN -28 and MKN- 45 and to investigate its possible mechanism. Methods Gastric carcinoma cell lines MKN -28 and MKN -45 cultured in vitro were treated by rapamycin and RADO01 (20 nmol/L), and then the cell Coulter Counter and flow cytometry were used to detect cell growth and cell cycle. Results Both rapamycin and RAD001 could inhibit the growth of gastric carcinoma cell lines MKN - 28 and MKN - 45 in a time - dependence manner. The inhibition percentage of rapamyein at G2 phase (72 h) was 23.40% and 36.26% , and that of RAD001 at G2 phase was 25.12% and 40.11%, respectively. The cell counts of MKN -28 and MKN -45 in RAD001 group had significant differences compared with those in the negative control group and DMSO control group ( P 〈 0.05 ). At Go phase or 24 h after RADO01 treatment, the cell cycles of MKN - 28 and MKN - 45 changed and the proportion of cells stagnating at G0 - G1 increased. In RADO01 group, the difference in MKN - 45 cell cycle was significant ( P 〈 0. 05 ) , while that in MKN - 28 cell cycle was insignificant ( P 〉 0.05 ) , as compared to the negative control and DMSO control groups. Conclusion Of the two drugs, RAD001 is more sensitive to MKN -28 and MKN -45, while of the two cell lines, MKN-45 is more sensitive to rapamycin and RAD001. The result suggests that RAD001 can inhibit the growth of gastric carcinoma cells by its adiustment to cell cycles.
出处 《徐州医学院学报》 CAS 2009年第11期755-758,共4页 Acta Academiae Medicinae Xuzhou
基金 江苏省教育厅自然科学基金(05KJD320234)
关键词 胃肿瘤 哺乳动物雷帕霉素靶点 MKN-28 MKN-45 雷帕霉素 RAD001 stomach neoplasms mammalian target of rapamycin MKN-28 MKN-45 rapamycin RAD001
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参考文献8

  • 1Fingar DC, Blenis J. Target of rapamycin (TOR) : an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression [J]. Oncogene, 2004, 23 (18) :3151 -3171.
  • 2潘智,张令强,蒋继志,贺福初.mTOR的研究进展[J].细胞生物学杂志,2006,28(3):395-398. 被引量:22
  • 3郑杰.mTOR信号途径与肿瘤[J].生命科学,2006,18(3):261-265. 被引量:20
  • 4Jiang BH, Liu LZ. Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment [ J]. Drug Resist Updat, 2008, 11(3) :63 -76.
  • 5Byun DS, Cho K, Ryu BK, et al. Frequent monoallelic deletion of PTEN and its reciprocal association with PIK3CA amplification in gastric carcinoma [J]. Int J Cancer, 2003, 104(3):318 - 327.
  • 6Ang KL, Shi DL, Keong WW, et al. Upregulated Akt signaling adjacent to gastric cancers: implications for screening and chemoprevention [ J ]. Cancer Lett, 2005, 225 ( 1 ) :53 - 59.
  • 7Velho S, Oliveira C, Ferreira A, et al. The prevalence of PIK3CA mutations in gastric and colon cancer [ J]. Eur J Cancer, 2005, 41(11) :1649 - 1654.
  • 8Kobayashi I, Semba S, Matsuda Y, et al. Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma [J]. Pathobiology, 2006, 7.3(1) :8 -17.

二级参考文献23

  • 1Robert H.Getzenberg.Commentary on: Mobley AJ, Lam YW, Lau KM, Pais VM, Lesperance JO, Steadman B, et al. Monitoring the serological Proteome Colon, the latest modality in prostate cancer detection. J Urol 2004; 172: 331-7.[J].Asian Journal of Andrology,2004,6(4):283-283. 被引量:94
  • 2Inoki K,Corradetti M N,Guan K L.Dysregulation of the TSC-mTOR pathway in human disease.Nat Genet,2005,37(1):19~24
  • 3Guertin D A,Sabatini D M.An expanding role for mTOR in cancer.Trends Mol Med,2005,11(8):353~361
  • 4Sarbassov D D,Guertin D A,Ali S M,et al.Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.Science,2005,307(5712):1098~1101
  • 5Hardie D G.The AMP-activated protein kinase pathwaynew players upstream and downstream.J Cell Sci,2004,117(Pt 23):5479~5487
  • 6Martin D E,Hall M N.The expanding TOR signaling network.Curr Opin Cell Biol,2005,17(2):158~166
  • 7Law B K.Rapamycin:an anti-cancer immunosuppressant? Crit Rev Oncol Hematol,2005,56(1):47~60
  • 8Shaw R J,Bardeesy N,Manning B D,et al.The LKB 1 tumor suppressor negatively regulates mTOR signaling.Cancer Cell,2004,6(1):91~99
  • 9Grewe M,Gansauge F,Schmid R M,et al.Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells.Cancer Res,1999,59(15):3581~3587
  • 10Rosenwald I B,Chen J J,Wang S,et al.Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis.Oncogene,1999,18(15):2507~2517

共引文献39

同被引文献25

  • 1黄赤兵,张银甫.雷帕霉素作用机制研究及在肾移植中的应用进展[J].中国药房,2006,17(7):547-549. 被引量:6
  • 2陈静君,任宏.COX-2选择性抑制剂的抗肿瘤作用研究进展[J].中国药房,2007,18(19):1508-1509. 被引量:2
  • 3司文秀,杨继章.非甾体类抗炎药的抗癌作用及机制[J].中国药房,2007,18(19):1510-1512. 被引量:4
  • 4Jemal A, Bray F,Center MM, et al. Global cancer statistics[J].CA Cancer J Clin,2011,61(2) :69-90.
  • 5Perez-Tenorio G,Stal O,Southeast Sweden Breast Cancer Group.Activation of AKT/PKB in breast cancer predicts a worse out-come among endocrine treated patients[J]. Br J Cancer, 2002 ,86?4):540-545.
  • 6Yamnik RL,Holz MK. mTOR/S6Kl and MAPK/RSK signalingpathways coordinately regulate estrogen receptor alpha serine167 phosphorylation[J]. FEBS Lett ,2010 ,584(1) : 124-128.
  • 7Yamnik RL,Digilova A,Davis DC,et al. S6 kinase 1 regulates es-trogen receptor alpha in control of breast cancer cell proliferation[J]. J Biol Chem,2009,284(10) :6361-6369.
  • 8Osaki M, Oshimura M,Ito H. PI3K-Akt pathway : its functions and al-terations in human cancer[J]. Apoptosis,2004,9(6) :667-676.
  • 9Baselga J,Semiglazov V, van Dam P, et al. Phase II randomizedstudy of neoadjuvant everolimus plus letrozole compared withplacebo plus letrozole in patients with estrogen receptor-positivebreast cancer[J]. J Clin Oncol, 2009 ,27(16) : 2630-2637.
  • 10Davies C, Godwin J, Gray R, et al. Relevance of breast cancerhormone receptors and other factors to the efficacy of adjuvanttamoxifen; patient-level meta-analysis of randomised trials [JJ.Lancet ,2011,378(9793) :771-784.

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