The Cancer Genome Atlas (TCGA) database was used to study the correlation between the KCNK9 expression level and the prognosis of colon cancer patients. HT29 and SW480 colon cancer cell lines were cultured to examine the inhibitory effects of KCNK9 and genistein on colon cancer in vitro, and a mouse model of colon cancer with liver metastasis was established to verify the inhibitory effect of genistein in vivo.
KCNK9 was overexpressed in colon cancer cells and was associated with a shorter Overall Survival (OS), a shorter Disease-Specific Survival (DFS), and a shorter Progression-Free Interval (PFI) of colon cancer patients. In vitro experiments showed that downregulation of KCNK9 or genistein application could suppress cell proliferation, migration, and invasion abilities, induce cell cycle quiescence, promote cell apoptosis, and reduce epithelial-mesenchymal transition of the colon cancer cell line. In vivo experiments revealed that silencing of KCNK9 or application of genistein could inhibit hepatic metastasis from colon cancer. Additionally, genistein could inhibit KCNK9 expression, thereby attenuating Wnt/β-catenin signaling pathway.
Genistein inhibited the occurrence and progression of colon cancer through Wnt/β-catenin signaling pathway that could be mediated by KCNK9.
方法:使用癌症基因组图谱(TCGA)数据库研究KCNK9表达水平与结肠癌患者预后之间的相关性。培养HT29和SW480结肠癌细胞系,以检测KCNK9和金雀异黄素对结肠癌的体外抑制作用。建立结肠癌肝转移小鼠模型,验证金雀异黄素的体内抑制作用。
结果:KCNK9在结肠癌细胞中过表达,并与较短的总生存期(OS)相关,较短的疾病特异性生存期(DFS),结肠癌患者的无进展间期(PFI)较短。体外实验表明,下调KCNK9或染料木素的应用可以抑制细胞增殖,迁移,和入侵能力,诱导细胞周期静止,促进细胞凋亡,并减少结肠癌细胞系的上皮-间质转化。体内实验表明,沉默KCNK9或应用染料木素可以抑制结肠癌的肝转移。此外,金雀异黄素可以抑制KCNK9的表达,从而减弱Wnt/β-连环蛋白信号通路。
结论:染料木素通过KCNK9介导的Wnt/β-catenin信号通路抑制结肠癌的发生和发展。