目的:酪氨酸蛋白激酶抑制剂,Genistein,可以抑制细胞的恶性转化,对各种类型的癌症有抗肿瘤作用。已经证明染料木素和KNCK9都可以抑制结肠癌。本研究旨在探讨金雀异黄素对结肠癌细胞的抑制作用及其与KCNK9表达水平的相关性。
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。
The tyrosine-protein kinase inhibitor, genistein, can inhibit cell malignant transformation and has an antitumor effect on various types of cancer. It has been shown that both genistein and KNCK9 can inhibit colon cancer. This research aimed to investigate the suppressive effects of genistein on colon cancer cells and the association between the application of genistein and
KCNK9 expression level.
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.