Ju Hongping, Li Yongxia, Xing Xiqian, Miao Xisong, Feng Yunping, Ren Yunhui, Qin Jing, Liu Dian, Chen Zihao, Yang Zhaoyu
School of Medicine, Kunming University, Kunming, China.
The Department of Respiratory Medicine, Second Ward, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Thorac Cancer. 2018 Mar;9(3):353-359. doi: 10.1111/1759-7714.12584. Epub 2018 Jan 8.
Breast cancer is the leading cause of cancer-related death in the world, and it is of great value to reveal the molecular mechanisms of breast cancer progression and develop new therapeutic targets.
Transwell assay is used to analyze the migration and invasion of breast cancer cells. Real-time PCR and western blotting assay are applied to detect the expression levels of epithelial-mesenchymal transition markers and the key members of Wnt/β-catenin and PI3K/AKT signaling pathways.
Manganese-12 acetate (Mn12Ac) significantly inhibited the migration and invasion of MCF7 and MDA-MB-231 breast cancer cells. Western blotting assay further showed that Mn12Ac significantly upregulated E-cadherin, and downregulated N-cadherin and vimentin. We further found that Mn12Ac reduced the mRNA expressions of epithelial-mesenchymal transition-associated transcription factors snail, slug, twist1, and ZEB1 using real-time PCR assay. Importantly, we further found that Mn12Ac significantly reduced the Wnt1 and β-catenin protein expressions, and suppressed the phosphorylation of PI3K and AKT in MCF7 and MDA-MB-231 breast cancer cells. Very interestingly, we also showed that Mn12Ac decreased the mRNA and protein expressions of programmed cell death ligand 1.
Taken together, our results suggested that Mn12Ac inhibited the migration, invasion, and epithelial-mesenchymal transition by regulating Wnt/β-catenin and PI3K/AKT signaling pathways in breast cancer.
乳腺癌是全球癌症相关死亡的主要原因，揭示乳腺癌进展的分子机制并开发新的治疗靶点具有重要价值。
采用Transwell实验分析乳腺癌细胞的迁移和侵袭能力。运用实时荧光定量PCR和蛋白质免疫印迹法检测上皮-间质转化标志物以及Wnt/β-连环蛋白和PI3K/AKT信号通路关键成员的表达水平。
乙酸锰-12（Mn12Ac）显著抑制MCF7和MDA-MB-231乳腺癌细胞的迁移和侵袭。蛋白质免疫印迹法进一步显示，Mn12Ac显著上调E-钙黏蛋白表达，下调N-钙黏蛋白和波形蛋白表达。通过实时荧光定量PCR实验，我们进一步发现Mn12Ac降低了上皮-间质转化相关转录因子蜗牛蛋白、蛞蝓蛋白、Twist1和锌指蛋白E盒结合因子1（ZEB1）的mRNA表达。重要的是，我们进一步发现Mn12Ac显著降低了MCF7和MDA-MB-231乳腺癌细胞中Wnt1和β-连环蛋白的蛋白表达，并抑制了PI3K和AKT的磷酸化。非常有趣的是，我们还发现Mn12Ac降低了程序性细胞死亡配体1的mRNA和蛋白表达。
综上所述，我们的结果表明Mn12Ac通过调节乳腺癌中的Wnt/β-连环蛋白和PI3K/AKT信号通路抑制细胞迁移、侵袭和上皮-间质转化。
