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

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...

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Bibliographic Details
Published in:Frontiers in pharmacology 2022-06, Vol.13, p.917827-917827
Main Authors: Tian, Wenjia, Hao, Huifeng, Chu, Ming, Gong, Jingjing, Li, Wenzhe, Fang, Yuan, Zhang, Jindong, Zhang, Cunzheng, Huang, Yonghui, Pei, Fei, Duan, Liping
Format: Article
Language:English
Subjects:
berberine
endothelial barrier
metastasis
pancreatic cancer
Pharmacology
TGFBR1
trans-endothelial migration
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Summary: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.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.917827