健脾复方通过Exo-Wnt3a/5a调控Wnt/β-catenin信号通路抑制大肠癌侵袭转移机制研究

Mechanism Research on Spleen Invigorating Recipe Regulating Wnt/β-catenin Signaling Pathway through Exo-Wnt3a/5a to Inhibit the Invasion and Metastasis of Colorectal Cancer

目的:探究大肠癌侵袭转移中健脾复方对Wnt3a/5a调控Wnt/β-catenin信号通路的作用机制。方法:建立裸鼠人肠癌转移瘤模型,使用低、中、高剂量的健脾复方进行治疗干预,同时设阳性对照组及空白对照组,收集裸鼠血清,并保留瘤体,使用WB检测Exo-Wnt3a/5a、β-catenin、MMP-7、C-MYC、CyclinD1等信号分子。结果:β-catenin、MMP-7、C-MYC、CyclinD1在健脾复方高剂量组中表达水平最低,β-catenin异常表达与MMP-7、C-MYC、CyclinD1在大肠癌肿瘤细胞中出现高表达有明显正相关性(P<0.05)。结论:健脾复方可下调Wnt3a/5a,从而降低大肠癌细胞的增殖、侵袭,并增加对Wnt/β-catenin信号通路的抑制作用,从而控制大肠癌的发展及转移。

Objective:To explore the mechanism of Spleen Invigorating Recipe on Wnt3a/5a regulation of Wnt/β-catenin signaling pathway in the invasion and metastasis of colorectal cancer. Methods: We established a nude mouse model of human colon cancer metastasis, and used low, medium, and high doses of Spleen Invigorating Recipe for therapeutic intervention. At the same time, a positive control group and a blank control group were set up. Nude mouse serum was collected and the tumor was preserved. WB detection was used to detect Exo-Wnt3a/5a, β-catenin, MMP-7, C-MYC, CyclinD1 and other signal molecules. Results: The expression levels of β-catenin, MMP-7, C-MYC, and CyclinD1 were the lowest in the high-dose Jianpi compound group. The abnormal expression of β-catenin and MMP-7, C-MYC, and CyclinD1 were high in colorectal cancer tumor cells. The expression had a significant positive correlation(P<0.05). Conclusion: Spleen Invigorating Recipe can down-regulate Wnt3a/5a, thereby reducing the proliferation and invasion of colorectal cancer cells, and increasing the inhibition of Wnt/β-catenin signaling pathway, so as to control the development and metastasis of colorectal cancer.