β-catenin在胃癌中的表达及其机制

Expression of β-catenin in gastric cancer and its mechanism

目的探讨Wnt信号通路中心调控分子β-catenin在胃癌中的表达及其在胃癌发病中的作用机制。方法利用shRNA病毒沉默BGC-823胃癌细胞株中的β-catenin的表达,利用空载病毒感染细胞株作为对照组,实时荧光定量PCR及Western blot检测病毒沉默效果,将转染后的细胞株注入裸鼠颈部构建裸鼠胃癌模型,每周检测2组裸鼠皮下肿瘤生长情况并测量记录皮下瘤块直径。成瘤裸鼠模型饲养8w后分离完整皮下瘤块,统计瘤块数量及瘤块重量。Western blot检测2组裸鼠皮下瘤块中Wnt信号通路相关分子DKK1、c-myc、CyclinD1的表达变化。结果β-catenin沉默后的BGC-823胃癌细胞株注射裸鼠,其皮下瘤块的数量、直径以及重量均较对照空载病毒转染的BGC-823胃癌细胞株注射的裸鼠少,差异具有统计学意义(P<0.05),且β-catenin沉默组裸鼠,其瘤块中DKK1、c-myc、CyclinD1的表达水平较对照组裸鼠显著降低(P<0.05)。结论β-catenin通过上调DKK1、c-myc、CyclinD1的表达促进胃癌细胞的增殖,因此β-catenin在胃癌发生发展过程中具有重要作用,其可能作为评估胃癌预后的诊断指标。

Objective To study the expression of β-catenin,key molecular of Wnt signaling pathway in gastric cancer and its mechnism.Methods Using shRNA virus to silence the expression of β-catenin in BGC-823 gastric cancer cell lines and using virus without shRNA as the control group. The silence effect of shRNA virus were detected by real-time quantitative flouorescence PCR and Western blot,then transfected into nude mice to construct gastric cancer nude mice model. The subcutaneous tumor growth situation（measure tumor diameter） were detected in two groups of nude mice model every week. After 8 weeks number and weight of subcutaneous tumor were recorded. The DKK1,c-myc and CyclinD1 related to Wnt signaling pathways in subcutaneous tumor in two groups of nude mice were detected by Western blot. Results After silence of β-catenin in BGC-823 gastric cancer cell lines,the number,diameter and weight of the subcutaneous tumor block in β-catenin were less than empty carrier control group,with statistically significant difference（P 〈0. 05）. The expression of DKK1,c-myc,CyclinD1 levels significantly reduced in β-catenin silent group of nude mice than control group（P 〈0. 05）. Conclusion β-catenin upregulates the expressions of DKK1,c-myc,CyclinD1 to promote gastric cancer cell proliferation,hence β-catenin plays an important role in the process of gastric cancer and it may be valuable diagnosis index in the prognosis of gastric cancer.