BACKGROUND Furowanin A (Fur A) is a flavonoid compound isolated from medicinal plant Millettia pachycarpa Benth. This study aims to explore the effect of Fur A on Colorectal cancer (CRC) and its molecular mechanisms. METHODS Cell proliferative capacity of CRC cells was assessed by CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell migration and invasion were detected by wound healing and Transwell assay, respectively. EMT markers, apoptosis and profilin 1(Pfn1) expression were detected by immunohistochemistry (IHC). The protein expression levels were examined by western blotting. i-TRAQ analyses were conducted to identify the differentially expressed genes in CRC cells. CRC xenograft model was also used to validate the in vivo anti-cancer activity of Fur A. RESULTS Fur A exhibited anti-prolifertive, blocked cell cycle progression and promoted apoptotic cell death in CRC cells. Fur A suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro, and tumor growth and pulmonary metastasis in vivo, without causing obvious toxicity. iTRAQ analysis identified Pfn1 as a gene up-regulated by Fur A. In xenograft tumor tissue, the expression of Pfn1 was also elevated by Fur A treatment. In clinical CRC samples, high expression of Pfn1 was correlated with lower stage and longer survival. Knockdown of Pfn1 significantly dampened the pro-apoptotic and anti-metastatic activities of Fur A in CRC cells. Ectopic Pfn1 expression augmented the anti-neoplastic activities of Fur A. CONCLUSION Fur A exhibited anti-cancer activities in vitro and in vivo in CRC by up-regulating Pfn1.

中文翻译：

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鉴定 profilin 1 作为 Furowanin A 在结直肠癌中抗癌活性的主要靶点。

背景Furowanin A (Fur A) 是从药用植物鸡血藤中分离出来的黄酮类化合物。本研究旨在探讨Fur A对结直肠癌（CRC）的影响及其分子机制。方法采用CCK-8法评估CRC细胞的细胞增殖能力。流式细胞术检测细胞凋亡和细胞周期分布。分别通过伤口愈合和Transwell实验检测细胞迁移和侵袭。免疫组织化学（IHC）检测EMT标志物、细胞凋亡和profilin 1（Pfn1）表达。通过蛋白质印迹检查蛋白质表达水平。进行 i-TRAQ 分析以确定 CRC 细胞中的差异表达基因。CRC 异种移植模型也用于验证 Fur A 的体内抗癌活性。结果 Fur A 在 CRC 细胞中表现出抗增殖、阻断细胞周期进程并促进细胞凋亡。Fur A 在体外抑制迁移、侵袭和上皮间质转化（EMT），在体内抑制肿瘤生长和肺转移，且不引起明显的毒性。iTRAQ 分析确定 Pfn1 是 Fur A 上调的基因。在异种移植肿瘤组织中，Fur A 处理也提高了 Pfn1 的表达。在临床 CRC 样本中，Pfn1 的高表达与较低的分期和较长的生存期相关。Pfn1 的敲除显着抑制了 Fur A 在 CRC 细胞中的促凋亡和抗转移活性。异位 Pfn1 表达增强了 Fur A 的抗肿瘤活性。结论 Fur A 通过上调 Pfn1 在体外和体内的 CRC 中表现出抗癌活性。