姜黄素通过Wnt信号转导通路抑制肺癌细胞A549增殖的研究

Curcumin inhibits proliferation of lung cancer cell A549 through Wnt signaling pathway

目的:从研究Wnt信号通路的关键因子-核蛋白β-catenin入手,探讨姜黄素(Curcumin,Cur)可能存在的抑制肺癌细胞增殖的分子学机制。方法:MTT法检测不同浓度的Cur对肺癌细胞A549的生长抑制情况,分析药物浓度和细胞增殖抑制率之间的关系;Western blot法检测Cur作用后,A549细胞核蛋白β-catenin含量的变化;RT-PCR方法验证Cur对细胞c-myc基因表达的影响;流式细胞仪观察经Cur作用后细胞周期的改变。结果:Cur以浓度依赖方式抑制肺癌细胞A549的增殖,该药物浓度与抑制率之间有明显的线性相关性(r=0.9333)。细胞经Cur干预48h后,核蛋白β-catenin的含量和促癌基因c-myc的表达含量均有所下降。流式细胞仪观察细胞周期的结果提示,Cur能够阻止肺癌细胞A549由G1期进入S期,提高G0/G1期细胞的百分比。结论:Cur能够抑制A549细胞胞浆内β-catenin蛋白进入胞核,阻断Wnt信号转导通路,进而抑制下游靶基因c-myc的表达,阻止肺癌细胞A549由G1期进入S期,有效抑制了A549细胞的增殖。

Objective： To explore the possible molecular mechanism of inhibiting the proliferation of lung cancer cells by studing curcumin regulating neucleoprotein β-catenin,the key factor of Wnt signaling pathway. Methods： Non-toxic different doses of curcumin affected human lung adenocarcinoma cell A549 for 48 hours.lnhibitory effect of curcumin on proliferation of A549 cells was evaluated by MTT assay.The correclation of doses and inhibition ratio was analyzed statistically.The neucleoprotein levels of β-catenin was analyzed by Western transcription-polymerase chain reaction（RT-PCR）.The exchange blot.The expression level of c-myc was analyzed by reverse of cell cycle was examined by flow cytometry（FCM）. Results： Curcumin inhibited the proliferation of A549 in a concentration-dependent manner（P〈0.05）,and there was obvious linear correlation between drug concentrations and inhibition ratio（r=0.933 3）.The expresson of nucleoprotein β-catenin and oncogene c-myc were all down-regulated in A549 cells（P〈0.05） after treatment with curcumin.Curcumin prevented A549 cells from G1 to S phase period,and raised the percentage of G0/G1 phase cells（P〈0.05）. Conclusion： Curcumin could prevent β-catenin protein of A549 cells into the nucleus from the cytoplasm,block Wnt signal transduction pathway and inhibit the expression of downstream target genes c-myc.Thereby,curcimin prevents lung cancer cells from G1 phase to S phase,and effectively inhibit the proliferation of A549 cells.