Axin通过负向调控Wnt通路抑制A549细胞系增殖

Axin inhibits the proliferation of A549 by negatively regulating Wnt pathway

目的:前期研究发现转染Axin能抑制A549细胞的增殖能力,本研究目的是探讨Axin抑制A549细胞增殖能力的机制。方法:我们构建了野生型和突变型Axin质粒(Axin与β-catenin结合位点剪切突变)转染A549细胞,并应用GSK-3βsiRNA处理细胞,Western bolt检测各处理组β-catenin和cyclin D1的变化,MTT检测各处理组细胞增殖能力的变化。结果:转染野生型Axin能够明显地下调β-catenin和cyclin D1(P<0.01),抑制Wnt通路活性和A549细胞的增殖(P<0.01),而GSK-3βsiRNA可以阻断Axin的这种功能;转染突变型Axin不能有效的下调Wnt通路或A549细胞的增殖能力。结论:Axin主要是通过负向调控Wnt通路抑制A549细胞的增殖。Axin可能成为未来治疗肺癌的新靶点。

Objective： We found that transfection of Axin could inhibit the proliferation of A549 cells, but the ex- act mechanism is unclear. Methods： We constructed wild - type Axin plasmid, Axin mutant （ β - catenin binding site shear mutation） and GSK- 3β siRNA to treat A549, Western blot was used to detect the expression of β -catenin and cyclin D1. MTT was used to study the change of proliferation. Results： Transfection of wild - type Axin down - regulated β -catenin and cyclin D1 （P 〈 0.05 ） and negatively regulated Wnt pathway and the proliferation of A549. GSK - 3β siRNA could block this function of Axin. Transfection of Axin mutant could not down - regulate Wnt path- way or the proliferation of A549. Conclusion：Axin inhibits the proliferation of 3.549 cells mainly through negatively regulating Wnt signaling. Axin may become a new target for clinical treatment of lung cancer.