Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1.

Abstract

Despite the remarkable clinical response in ovarian cancer therapy, the distinctively high metastasis rate is still a barrier to achieve satisfying prognosis. Our study aimed to decipher the role of berberine in inhibiting chemotherapy-exacerbated ovarian cancer metastasis. We found that chemotherapy exacerbated the migration and cancer stem cell (CSC)-like characteristics through transcriptional factor GLI1, which regulated the pluripotency-associated gene BMI1 and the epithelial-mesenchymal transition (EMT) markers Vimentin and Snail. Berberine could not only down-regulate CSC-like characteristics but also reverse EMT and migration through inhibiting chemotherapy-activated GLI1/BMI1 signaling pathway. Together, our study revealed the pivotal role of berberine in overcoming chemotherapy-exacerbated ovarian cancer metastasis, thereby provided a potential adjuvant therapeutic agent in combination with chemotherapeutics to prevent metastasis during ovarian cancer chemotherapy.

• Authors: Yawei Zhao, Xuehan Yang, Jingtong Zhao, Mohan Gao, Min Zhang, Tongfei Shi, Fan Zhang, Xiao Zheng, Yue Pan, Dan Shao, Jing Li, Kan He, Li Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 895 Pg. 173887 (Mar 15 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 33482182 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• BMI1 protein, human
• GLI1 protein, human
• SNAI1 protein, human
• Snail Family Transcription Factors
• VIM protein, human
• Vimentin
• Zinc Finger Protein GLI1
• Berberine
• Etoposide
• Carboplatin
• Polycomb Repressive Complex 1

Topics

• Antineoplastic Agents (toxicity)
• Berberine (pharmacology)
• Carboplatin (toxicity)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Coculture Techniques
• Epithelial-Mesenchymal Transition (drug effects)
• Etoposide (toxicity)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Metastasis
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• Polycomb Repressive Complex 1 (genetics, metabolism)
• Signal Transduction
• Snail Family Transcription Factors (genetics, metabolism)
• Vimentin (genetics, metabolism)
• Zinc Finger Protein GLI1 (genetics, metabolism)