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索拉菲尼对人胃癌细胞SGC-7901增殖、凋亡和P-ERK表达的影响 被引量:2

The effect of sorafenib on growth,apoptosis and P-ERK expression in human gastric cancer SGC-7901 cells
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摘要 目的探讨多分子靶向药物索拉菲尼(sorafenib)对体外人胃癌细胞SGC-7901增殖、凋亡的影响及对癌细胞P-ERK表达的影响,并探讨其可能机制。方法以MTT法检测索拉菲尼对SGC-7901细胞的杀伤抑制作用;免疫细胞化学法检测胃癌细胞内P-ERK蛋白的表达;流式细胞仪检测胃癌细胞凋亡的变化情况。结果索拉菲尼对胃癌细胞生长增殖具有抑制作用,随药物浓度的增加作用也增强,呈剂量—时间双效应关系(P<0.05);经索拉菲尼处理的SGC-7901细胞的P-ERK表达明显下降(P<0.05);细胞凋亡率增高(P<0.05)。结论 sorafenib在体外对SGC-7901细胞具有明显的抑制作用,主要机制为抑制其P-ERK表达,从而抑制其增殖和促进凋亡。 Objective To investigate the multiple molecular targeted agent,sorafenib,in human gastric cancer SGC-7901 cell proliferation,apoptosis and P-ERK expression,and explore its possible mechanism.Methods MTT method was used to detect antiproliferative ratio of sorafenib on human gastric cancer SGC-7901 cell;immunocytochemical method for detection of gastric cancer cells P-ERK protein expression;and flow cytometry to analyze gastric cancer cell apoptosis.Results Sorafenib obviously inhibited proliferation of gastric cancer cells and showed time-dose-dependent effects(P0.05).When gastric cancer SGC-7901 cells were treated with sorafenib,immunocytochemistry showed that P-ERK expression was significantly decreased(P0.05);flow cytometry showed that the SGC-7901 cell apoptosis rate increased(P0.05).Conclusions Sorafenib can significantly inhibit human gastric cancer SGC-7901 cell growth in vitro;the main mechanism is the inhibition of P-ERK expression,and thereby inhibit their proliferation and promote apoptosis.
出处 《中国普通外科杂志》 CAS CSCD 北大核心 2011年第4期367-371,共5页 China Journal of General Surgery
关键词 胃肿瘤/病理学 索拉菲尼 SGC-7901细胞 细胞增殖 细胞凋亡 P-ERK 流式细胞术 Stomach Neoplasms/pathol Sorafenib SGC-7901 Cells Cell Proliferation Apoptosis P-ERK Flow Cytometry
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参考文献14

  • 1Roberts PJ, Der CJ. Targeting the Raf-MEK-ERK mitogenactivated protein kinase cascade for the treatment of cancer [ J ] . Oncogene ,2007,26 (22) :3291 - 3310.
  • 2Wong KK. Recent developments in anticancer agents targeting the Ras /Raf /MEK/ERK pathway [ J ] . Recent Pat Anticancer Drug Discov, 2009,4 (1) :28 -35.
  • 3李宗海.Ras/Raf/MEK/Erk通路调控细胞功能的机制[J].国外医学(生理病理科学与临床分册),2000,20(1):12-14. 被引量:14
  • 4Bokemeyer O, Sorokin A, Dunn MJ, et al. Multiple intracellular MAP kinase signaling cascades [ J ]. Kindey Int, 1996,49 (5) :1187 -1198.
  • 5Jin S, Zhou Y, Guo W, et al. P21-activated Kinase 1 ( Pak 1 ) -dependent Phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 Association [ J ]. J Biol Chem, 2005,280 ( 26 ) : 24698 -24705.
  • 6Yoo J, Park SY, Robinson RA, et al. Ras gene mutations and expression of Ras signal transduction mediators in gastric adenocarcinomas [ J ]. Arch Pathol Lab Med, 2002,126 ( 9 ) : 1096 - 1100.
  • 7Iwase T, Tanaka M, Suzuki M, et al. Identification of proteintyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer [ J ]. Biochem Biophys Res Commun, 1993,194 (2) :698 -705.
  • 8Bang YJ, Kwon JH, Kang SH, et al. Increased MAPK activity and MKP-1 overexpression in human gastric adenocarcinoma [ J]. Biochem Biophys Res Commun, 1998,250 (1):43 -47.
  • 9Wilhelm SM,Carter C, Tang L,et al. BAY 43 -9006 exhibits broad Spectrum oral antitumor activity and targets the RAS/RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis [ J ]. Cancer Res ,2004,64(19) :7099 -7109.
  • 10Strumberg D. Preclinical and clinical development of the oral muhikinase inhibitor sorafenib in cancer treatment [ J ]. Drugs Today (Barc) ,2005,41(12) :773 -784.

二级参考文献20

  • 1White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer[J]. Clin Cancer Res,2009, 15(17):5308-5316.
  • 2Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocel|ular carcinoma [J]. N Engl J Med, 2008,359(4):378-390.
  • 3He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy[J]. Annu Rev Genet,2009,43:67- 93.
  • 4Liu L, Cao Y, Chert C, et al. Sorafenib blocks the RAF/ MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5 [J]. Cancer Res,2006,66 (24):11851- 11858.
  • 5Sivaprasad U, Basu A. Inhibition of ERK attenuates autophagy and potentiates turnout necrosis factor induced cell death in MCF-7 cells [J]. J Cell Mol Med, 2008,12(4): 1265-1271.
  • 6Chang CP, Yang MC, Liu HS, et al. Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a routine in situ hepatoma model[J]. Hepatology,2007,45(2):286-296.
  • 7Gao M, Yeh PY, Lu YS, et al. OSU-03012, a novel celecoxib derivative, induces reactive oxygen species- related autophagy in hepatocellular carcinoma[J]. Cancer Res,2008,68(22):9348-9357.
  • 8Brech A, Ahlquist T, Lothe RA, et al. Autophagy in turnout suppression and promotion[J]. Mol Oncol 2009,3 (4):366-375.
  • 9Longo L, Platini F, Scardino A, el al. Autophagy inhibition enhances anthocyanin-inducecl apoptosis in hepatocellular carcinoma[J]. Mol Cancer Ther,2008,7(8): 2476-2485.
  • 10Luo S, Rubinsztein DC. Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy[J]. Cell Death Differ,2007,14(7):1247-1250.

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