Matrine restrains the development of colorectal cancer through regulating the AGRN/Wnt/β‐catenin pathway

Abstract

AbstractBackgroundColorectal cancer is a common malignant digestive tract tumor. This study aimed to explore the biological role and potential underlying mechanism of matrine in colorectal cancer.MethodsThe mRNA expression of AGRN was measured using RT‐qPCR. Cell proliferation, migration, invasion and apoptosis were determined using CCK‐8, EdU, transwell assays and flow cytometry, respectively. Xenograft tumor experiment was performed to explore the action of matrine and AGRN on tumor growth in colorectal cancer in vivo. Immunohistochemistry (IHC) assay was applied for AGRN, β‐catenin, and c‐Myc expression in the tumor tissues from mice.ResultsMatrine dramatically repressed cell growth and reduced the level of AGRN in colorectal cancer cells. AGRN expression was boosted colorectal cancer tissues and cells. AGRN downregulation depressed cell proliferation, migration, invasion, and enhanced cell apoptosis in colorectal cancer cells. Moreover, matrine showed the anti‐tumor effects on colorectal cancer cells via regulating AGRN expression. AGRN knockdown could inactivate the Wnt/β‐catenin pathway in colorectal cancer cells. We found that AGRN downregulation exhibited the inhibition action in the progression of colorectal cancer by modulating the Wnt/β‐catenin pathway. In addition, matrine could inhibit the activation of the Wnt/β‐catenin pathway through regulating AGRN in colorectal cancer cells. Furthermore, xenograft tumor experiment revealed that matrine treatment or AGRN knockdown repressed the development of colorectal cancer via the Wnt/β‐catenin pathway in vivo.ConclusionMatrine retarded colorectal cancer development by modulating AGRN to inactivate the Wnt/β‐catenin pathway.