Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

Xuan Liu; Qing Ji; Naijing Ye; Hua Sui; Lihong Zhou; Huirong Zhu; Zhongze Fan; Jianfeng Cai; Qi Li

doi:10.1371/journal.pone.0123478

Berberine Inhibits Invasion and Metastasis of Colorectal Cancer Cells via COX-2/PGE2 Mediated JAK2/STAT3 Signaling Pathway

PLoS One. 2015 May 8;10(5):e0123478. doi: 10.1371/journal.pone.0123478. eCollection 2015.

Authors

Xuan Liu¹, Qing Ji¹, Naijing Ye¹, Hua Sui¹, Lihong Zhou¹, Huirong Zhu¹, Zhongze Fan², Jianfeng Cai³, Qi Li¹

Affiliations

¹ Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Interventional Cancer Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Department of Chemistry, University of South Florida, Tampa, Florida, United States of America.

Abstract

Berberin, extracted from Chinese herbal medicine Coptis chinensis, has been found to have anti-tumor activities. However, the underlying mechanisms have not been fully elucidated. Our current study demonstrated that berberin inhibited the in vitro and in vivo growth, migration/invasion of CRC cells, via attenuating the expression levels of COX-2/PGE2, following by reducing the phosphorylation of JAK2 and STAT3, as well as the MMP-2/-9 expression. We further clarified that an increase of COX-2/PGE2 expression offset the repressive activity of Berberin on JAK2/STAT3 signaling, and a JAK2 inhibitor AZD1480 blocked the effect of COX-2/PGE2 on MMP-2/-9 expression. In summary, Berberin inhibited CRC invasion and metastasis via down-regulation of COX-2/PGE2- JAK2/STAT3 signaling pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology
Antineoplastic Agents, Phytogenic / therapeutic use*
Berberine / chemistry
Berberine / pharmacology
Berberine / therapeutic use*
Cell Line, Tumor
Cell Movement / drug effects*
Colon / drug effects
Colon / metabolism
Colon / pathology
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / pathology
Coptis / chemistry
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Dinoprostone / genetics
Dinoprostone / metabolism
Gene Expression Regulation, Neoplastic / drug effects
Humans
Janus Kinase 2 / genetics
Janus Kinase 2 / metabolism
Male
Mice, Inbred BALB C
Neoplasm Invasiveness / genetics
Neoplasm Invasiveness / pathology
Neoplasm Invasiveness / prevention & control*
Neoplasm Metastasis / drug therapy*
Neoplasm Metastasis / genetics
Neoplasm Metastasis / pathology
Rectum / drug effects
Rectum / metabolism
Rectum / pathology
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects*

Substances

Antineoplastic Agents, Phytogenic
STAT3 Transcription Factor
Berberine
Cyclooxygenase 2
Janus Kinase 2
Dinoprostone

Grants and funding

This work was supported by the National Natural Science Foundation of China (81303103, 81473478, 81303102), Science and Technology Commission of Shanghai Municipality (13ZR1461000, 14140901402) and Program of Shanghai Municipal Education Commission (13CG47, 13YZ045). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.