Despite significant advances in the diagnosis and treatment of colorectal cancer (CRC), metastatic colorectal cancer still poses serious threat to CRC patients. The natural gallotannin 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been shown to possess anti-tumor effects on colon cancer cells, but its anti-metastatic effect is yet to be investigated. In this study, the effects of PGG on cell proliferation, colony formation ability, motility, migration were investigated in colon cancer cells using BrdU, colony formation, scratch, and transwell assays, respectively. Western blot assay was used for assessing protein expression. The orthotopic colon tumor-bearing mouse model and human colon cancer metastatic mouse model were employed to evaluate the anti-metastatic effects of PGG. Results showed that PGG exhibited not only anti-proliferative and colony formation inhibitory effects, but also inhibition on cell adhesion, motility, and migration in both HCT116 and colon 26-M01 cells via modulating protein expression of cathepsin B, FAK, cofilin, and epithelial-to-mesenchymal transition related proteins. In addition, PGG (10 or 15 mg/kg, i.p.) could significantly inhibit liver and lung metastasis in colon cancer metastatic mice models. Furthermore, PGG could regulate the populations of T cells, macrophages, and MDSCs, while the levels of IL-2, IL-6, IL-10, IFN-γ, and TNF-α were altered after PGG treatment in metastatic CRC mice. This is the first report of the anti-metastatic effects of PGG by regulating cathepsin B-mediated extracellular matrix dynamics and epithelial-to-mesenchymal transition process in CRC. Our findings suggested that PGG has great potential to be developed as an anti-metastatic agent for metastatic CRC.

尽管结直肠癌（CRC）的诊断和治疗取得了重大进展，但转移性结直肠癌仍然对结直肠癌患者构成严重威胁。天然没食子单宁1,2,3,4,6-五-O-没食子酰-β- D-葡萄糖（PGG）已被证明对结肠癌细胞具有抗肿瘤作用，但其抗转移作用尚未得到证实。被调查。在这项研究中，分别使用 BrdU 、集落形成、划痕和 transwell 测定法研究了 PGG 对结肠癌细胞中细胞增殖、集落形成能力、运动性和迁移的影响。蛋白质印迹测定用于评估蛋白质表达。原位结肠荷瘤小鼠模型和人采用结肠癌转移小鼠模型评价PGG的抗转移作用。结果表明，PGG不仅表现出抗增殖和集落形成抑制作用，而且通过调节组织蛋白酶B、 FAK、cofilin和上皮细胞的蛋白表达，抑制HCT116和结肠26-M01细胞的细胞粘附、运动和迁移。间质转化相关蛋白。此外，PGG（10 或 15 mg/kg， ip.) 可显着抑制结肠癌转移小鼠模型的肝肺转移。此外，PGG 可以调节 T 细胞、巨噬细胞和 MDSC 的数量，而在 PGG 治疗转移性 CRC 小鼠后，IL-2、IL-6、IL-10、IFN-γ 和 TNF-α 的水平发生了改变。这是PGG通过调节CRC中组织蛋白酶B介导的细胞外基质动力学和上皮-间质转化过程而发挥抗转移作用的第一份报告。我们的研究结果表明，PGG 有很大的潜力被开发为转移性 CRC 的抗转移剂。