The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Pharmacol Rep. 2019 Oct;71(5):940-949. doi: 10.1016/j.pharep.2019.05.007. Epub 2019 May 30.
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.
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.
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.
Fur A exhibited anti-cancer activities in vitro and in vivo in CRC by up-regulating Pfn1.
紫檀芪 A（Fur A）是从药用植物密花豆Millettia pachycarpa Benth 中分离得到的一种黄酮类化合物。本研究旨在探讨紫檀芪 A 对结直肠癌（CRC）的作用及其分子机制。
通过 CCK-8 法评估 CRC 细胞的增殖能力。通过流式细胞术检测细胞凋亡和细胞周期分布。通过划痕愈合和 Transwell 测定分别检测细胞迁移和侵袭。通过免疫组织化学（IHC）检测 EMT 标志物、凋亡和 Profilin 1（Pfn1）表达。通过 Western blot 检测蛋白表达水平。通过 iTRAQ 分析鉴定 CRC 细胞中差异表达的基因。还建立了 CRC 异种移植模型以验证 Fur A 的体内抗癌活性。
Fur A 在 CRC 细胞中表现出抗增殖、阻断细胞周期进展和促进细胞凋亡的作用。Fur A 在体外抑制迁移、侵袭和上皮间质转化（EMT），并在体内抑制肿瘤生长和肺转移，但没有引起明显的毒性。iTRAQ 分析鉴定出 Pfn1 是 Fur A 上调的基因。在异种移植肿瘤组织中，Fur A 处理也上调了 Pfn1 的表达。在临床 CRC 样本中，Pfn1 的高表达与较低的分期和更长的生存时间相关。敲低 Pfn1 显著减弱了 Fur A 在 CRC 细胞中的促凋亡和抗转移活性。过表达 Pfn1 增强了 Fur A 的抗肿瘤活性。
Fur A 通过上调 Pfn1 在体外和体内表现出抗 CRC 活性。
