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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Published inFrontiers in pharmacology Vol. 13; p. 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 Journal Article
LanguageEnglish
Published Frontiers Media S.A 16.06.2022
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.
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These authors have contributed equally to this work
This article was submitted to Pharmacology of Anti-Cancer Drugs, a section of the journal Frontiers in Pharmacology
Edited by: Zhiqiang Meng, Fudan University, China
Reviewed by: Hor Yue Tan, Hong Kong Baptist University, Hong Kong SAR, China
Chen Jue, Yangzhou University, China
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.917827