生长抑素对结肠癌细胞β-catenin和E-cadherin蛋白表达的影响  

Effect of somatostatin on the expression of β-catenin and E-cadherin in cultured human colon cancer cell lines

作　　者：杨杰[1] 梁庆模[2] 尚现章[1] 章跃民[1] 

机构地区：[1]武警广东总队医院普外科,广东广州510507 [2]南华大学附属南华医院普外科,湖南衡阳421001

出　　处：《武警医学院学报》2009年第5期439-441,447,F0002,共5页Acta Academiae Medicinae CPAPF

基　　金：湖南省自然科学基金项目(07JJ6158)

摘　　要：【目的】研究八肽生长抑素奥曲肽(octreotide,OCT)对体外培养的人结肠癌SW480细胞-βcatenin蛋白和E-cadherin蛋白表达的影响,初步探讨生长抑素(Somatostatin,SS)抑制Wnt信号通路的分子机制。【方法】以人结肠癌SW480细胞为研究对象,应用免疫细胞化学检测OCT10-10M处理SW480细胞48 h后,细胞-βcatenin蛋白表达及分布的变化;应用Western blotting检测OCT0、10-14、10-12、10-10M处理SW480细胞0、12、24、48 h后,细胞-βcatenin、E-cadherin蛋白表达的变化。【结果】经OCT处理后,免疫细胞化学检测结果显示:-βcatenin蛋白在细胞质、细胞核的表达显著降低,胞膜表达轻度增加;Western blotting检测结果显示:-βcatenin总蛋白表达显著下降,E-cadherin蛋白表达上调,二者均呈剂量和时间依赖性(P<0.01,P<0.05)。【结论】SS主要通过促进-βcatenin蛋白降解,其次是通过上调E-cadherin蛋白使-βcatenin膜定位增加,从而下调-βcatenin蛋白表达并抑制其核转录活性,这可能是SS抑制Wnt信号通路的重要分子机制。[ Objective] To study the effect of OCT on the expression of β-catenin and E-cadherin in cultured human colon cancer cell lines in order to initially elucidate the molecular mechanism of SS inhibiting Wnt pathway. [Methods] After treatment of OCT with 10^-10M for 48 h, β-Catenin expression and distribution were detected by immunocytochemiscal staining After SW480 cells were treated with OCT at various concentration of 0, 10^-14, 10^-12, 10^10 for 0, 12, 24, 48 h, β-Catenin and E-cadherin expression were assayed by Western blot analysis in SW480 cells. [ Results] After OCT treatment, Western blot analysis indicated that the exression of β-catenin total proteins reduced remarkably and the expression of E-cadherin protein enhanced. The changes in expression were dose and time dependent （ P 〈 0.01 and P 〈 0.05, respectively） . Immunocytochemical stain indicated that the expression of β-catenin in nucleus and cytoplasm was significant depressed, but in cell membrane the expression was increased a litfie. [ Conclusions] SS can downrngulate the expression of β-catenin and inhibit the trauscription activity of β-catenin, which may be the important molecular mechanism in SS inhibiting Wnt pathway. The molecular mechanisms include two aspects： the chief aspect is that SS promotes β-catenin degradation;the secondary aspect is that SS upregulates the expression of E-cadherin meanwhile increases the translocation of β-catenin to plasma membrane.

关 键 词：生长抑素 结肠癌β-catenin E-CADHERIN WNT通路 

分 类 号：R735.3[医药卫生—肿瘤]