亚硒酸钠对结直肠癌HCT 116和SW480细胞中β-catenin及下游靶基因cyclin D1表达的影响  

Effects of Sodium Selenite on the Expressions of β-catenin and Its Target cyclin D1 in Colorectal Cancer Cells HCT 116 and SW480

作　　者：罗慧[1] 杨洋[1] 许彩民[1] 

机构地区：[1]中国医学科学院北京协和医学院基础医学研究所医学分子生物学国家重点实验室,北京100005

出　　处：《中国医学科学院学报》2011年第6期654-658,共5页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(31170788;30970655);国家青年科学基金(31101018);北京市自然科学基金(5082015);国家重点实验室专项经费(2060204)~~

摘　　要：目的研究亚硒酸钠对结直肠癌HCT116和SW480细胞中β-catenin及下游靶基因cyclin D1表达的影响。方法采用10μmol/L亚硒酸钠处理HCT116和SW480细胞,Western blot及RT-PCR检测亚硒酸钠处理后不同时间HCT116和SW480细胞中β-catenin和cyclin D1的表达情况,并观察蛋白酶体抑制剂MG132预处理后对HCT116和SW480细胞中β-catenin和cyclin D1表达的影响。采用免疫共沉淀方法检测亚硒酸钠对HCT116和SW480细胞中β-catenin与T细胞因子4(TCF4)相互作用的影响。结果亚硒酸钠可降低HCT116和SW480细胞中β-catenin和cyclin D1的表达水平,用蛋白酶体抑制剂MG132预处理可增加亚硒酸钠处理后HCT116和SW480细胞中β-catenin和cyclin D1的表达水平。免疫共沉淀实验结果显示,亚硒酸钠能破坏β-catenin与TCF4间的相互作用。结论亚硒酸钠可降低结直肠癌HCT116和SW480细胞中β-catenin及cyclin D1的表达水平,蛋白酶体介导的降解途径可能在这一过程中发挥了重要作用。亚硒酸钠引起的β-catenin与TCF4相互作用减少可能对β-catenin靶基因的转录也起到了一定的调控作用。Objective To explore the effects of sodium selenite on the expressions of β-catenin and cyclin D1 in colorectal cancer cells HCT 116 and SW480.Methods HCT 116 and SW480 cells were treated by 10μmol/L sodium selenite at different time points.The expressions and transcription of β-catenin and cyclin D1 were detected by Western blot analysis and reverse transcriptase polymerase chain reaction（RT-PCR）,respectively.Meanwhile,the impact of MG132（a proteasome inhibitor） pretreatment on the expressions of β-catenin and cyclin D1 was observed through Western blot analysis.The interaction between β-catenin and T cell factor 4（TCF4） after selenite treatment was evaluated using co-immunoprecipitation assay.Results Sodium selenite inhibited the expression of β-catenin and transcription of its target such as cylcin D1.MG132 pretreatment prevented the inhibition of β-catenin signaling triggered by selenite in HCT 116 and SW480 cells.Furthermore,selenite treatment disrupted the interaction between β-catenin and TCF4 in HCT 116 and SW480 cells.Conclusions Sodium selenite can lower the expression levels of β-catenin and its target cyclin D1,during which the proteasome-mediated degradative pathway may be involved.The decreased interaction between β-catenin and TCF4 due to sodium selenite may be also involved in the regulation of β-catenin signaling.

关 键 词：亚硒酸钠 结直肠癌 Β-CATENIN cyclin D1 

分 类 号：Q735[生物学—分子生物学]