Berberine Suppresses Lung Metastasis of Cancer via Inhibiting Endothelial Transforming Growth Factor Beta Receptor 1

作者：Wenjia Tian, Huifeng Hao, Ming Chu, Jingjing Gong, Wenzhe Li, Yuan Fang, Jindong Zhang, Cunzheng Zhang, Yonghui Huang, Fei Pei, Liping Duan · 发表于：Frontiers in Pharmacology · 年份：2022 · DOI：10.3389/fphar.2022.917827 · 被引用次数：12 · 研究领域：Berberine and alkaloids research、Caveolin-1 and cellular processes、Synthesis and Biological Activity

This study investigated the effects of berberine (BBR) on pancreatic cancer (PC) lung metastasis and explored the underlying mechanisms, using a BALB/C-nu/nu nude mouse model injected with PC cells (AsPC-1). Intragastric administration of BBR dose-dependently improves survival of mice intravenously injected with AsPC-1 cells, and reduces lung metastasis. Especially, BBR significantly reduces lung infiltration of circulating tumor cells (CTCs) 24 h after AsPC-1 cells injection. In vitro , tumor cells (TCs) trigger endothelial barrier disruption and promote trans-endothelial migration of CFSE-labeled TCs. BBR treatment effectively ameliorates TC-induced endothelial disruption, an effect that is diminished by inhibiting transforming growth factor-β receptor 1 (TGFBR1). Blocking TGFBR1 blunts the anti-metastatic effect of BBR in vivo . Mechanistically, BBR binds to the intercellular portion of TGFBR1, suppresses its enzyme activities, and protects endothelial barrier disruption by TCs which express higher levels of TGF-β1. Hence, BBR might be a promising drug for reducing PC lung metastasis in clinical practice.