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

Wnt信号通路 苦参碱 结直肠癌 癌症研究 连环素 下调和上调 细胞生长 癌症 基因敲除 细胞凋亡 生物 医学 化学 信号转导 内科学 细胞生物学 精神科 基因 生物化学
作者
Xianzhe Li,Ye Lu,Penghao Wen,Yan Yuan,Zhenghong Xiao,Hengwei Shi,Eryan Feng
出处
期刊:Environmental Toxicology [Wiley]
卷期号:38 (4): 809-819 被引量:11
标识
DOI:10.1002/tox.23730
摘要

Abstract Background Colorectal 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. Methods The 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. Results Matrine 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. Conclusion Matrine retarded colorectal cancer development by modulating AGRN to inactivate the Wnt/β‐catenin pathway.
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