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

Wenjia Tian; Wenjia Tian; Huifeng Hao; Ming Chu; Jingjing Gong; Wenzhe Li; Yuan Fang; Jindong Zhang; Cunzheng Zhang; Yonghui Huang; Fei Pei; Liping Duan

doi:10.3389/fphar.2022.917827

Frontiers in Pharmacology (Jun 2022)

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

Wenjia Tian,
Wenjia Tian,
Huifeng Hao,
Ming Chu,
Jingjing Gong,
Wenzhe Li,
Yuan Fang,
Jindong Zhang,
Cunzheng Zhang,
Yonghui Huang,
Fei Pei,
Liping Duan

Affiliations

Wenjia Tian: Department of Gastroenterology, Peking University Third Hospital, Beijing, China
Wenjia Tian: Department of Gastroenterology, Peking University International Hospital, Beijing, China
Huifeng Hao: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education Beijing), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital and Institute, Beijing, China
Ming Chu: Department of Immunology, School of Basic Medical Sciences, Peking University, NHC Key Laboratory of Medical Immunology (Peking University), Beijing, China
Jingjing Gong: Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China
Wenzhe Li: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China
Yuan Fang: Department of Gastroenterology, Peking University Third Hospital, Beijing, China
Jindong Zhang: Department of Gastroenterology, Peking University Third Hospital, Beijing, China
Cunzheng Zhang: Department of Gastroenterology, Peking University Third Hospital, Beijing, China
Yonghui Huang: Department of Gastroenterology, Peking University Third Hospital, Beijing, China
Fei Pei: Department of Pathology, Peking University Third Hospital, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
Liping Duan: Department of Gastroenterology, Peking University Third Hospital, Beijing, China

DOI: https://doi.org/10.3389/fphar.2022.917827
Journal volume & issue: Vol. 13

Abstract

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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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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