Curcumin通过Wnt信号通路抑制乳腺癌细胞MCF-7增殖的研究

目的 观察姜黄素(Curcumin)对乳腺癌细胞MCF-7增殖的影响,以及对细胞内Wnt信号通路的影响,探索Curcumin可能存在的抑制乳腺癌细胞增殖的分子机制.方法 体外培养人乳腺癌细胞MCF-7,并用不同浓度的Curcumin作用不同的时间.用MTT检测Curcumin对MCF-7细胞生长情况的影响;流式细胞仪观察经Curcumin作用后细胞周期的改变;RT-PCR和Westernblot分别检测细胞内β -catenin和下游靶基因CyclinD1的mRNA和蛋白水平的表达.结果 MTT结果显示Curcumin可以抑制MCF-7的增殖,并具有剂量-时间依赖性.在浓度为20 μmol·L-1时,对细胞生长的抑制作用最为明显.流式细胞仪观察细胞周期的结果提示,Curcumin能够阻止MCF-7细胞由G1期进入S期,提高Go/G1期细胞的百分比.RT-PCR和Western blot结果显示,Curcumin显著降低了细胞内β-catenin和CyclinD1的mRNA和蛋白水平的表达,且呈剂量-时间依赖性.结论 Curcumin能够抑制MCF-7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CyclinD1的表达,阻止MCF-7由G1期进入S期,有效抑制了MCF-7细胞的增殖.

Inhibitory Effect of Curcumin on Human Breast Cancer Cells MCF-7 Proliferation through Wnt Signaling Pathway

Objective To observe the inhibitory effect of curcumin on human breast cancer cells MCF-7 in vitro, and to detect the effect on Wnt signaling pathway,and to explore its possible molecular mechanisms. Methods Human breast cancer cells MCF-7 were cultured and treated with curcumin at different concentration and at different time points. The effects of curcumin on MCF-7 cells proliferation was studied by means of MTT. The exchange of cell cycle was examined by flow cytometry （FCM）. RT-PCR and western blot were used to detect the expression of β-catenin and its downstream gene CyclinD1 at mRNA and protein levels. Results The proliferation of MCF-7 cells treated with curcumin was obviously decreased, and it was in a concentration- and time-dependent manner. The inhibitory effect of Curcumin was the most sig- nificant at the concentration of 20 μmol. L^-1. Curoumin prevented MCF-7 ceils from G1 to S phase period, and raised the percentage of Go/ G1 phase cells （ P 〈 0.05 ）. RT-PCR and Western blot results showed that the expression of 13-catenin and CyclinD1 at mRNA and protein levels were inhibited by curcumin in a concentrationand time-dependent manner （ P 〈 0.05 ）. Conclusion Curcumin could prevent β-catenin of MCF-7 into the nucleus from the cytoplasm, and block Wnt signaling pathway, and inhibit the expression of its downstream target gene CyclinD1. Thereby, curcumin prevents breast cancer ceils MCF-7 from G1 phase to S phase, and inhibits the proliferation of MCF-7 cells, which will provide an important therapeutic mechanism for treating with breast cancer.