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

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

doi:10.1016/j.ejphar.2021.173887

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

Eur J Pharmacol. 2021 Mar 15:895:173887. doi: 10.1016/j.ejphar.2021.173887. Epub 2021 Jan 20.

Authors

Yawei Zhao¹, Xuehan Yang¹, Jingtong Zhao¹, Mohan Gao¹, Min Zhang¹, Tongfei Shi¹, Fan Zhang¹, Xiao Zheng¹, Yue Pan¹, Dan Shao², Jing Li¹, Kan He³, Li Chen⁴

Affiliations

¹ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China.
² Institutes of Life Sciences, School of Biomedical Sciences and Engineering and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 510006, People's Republic of China.
³ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China. Electronic address: [email protected].
⁴ Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China; School of Nursing, Jilin University, Changchun 130021, People's Republic of China. Electronic address: [email protected].

PMID: 33482182
DOI: 10.1016/j.ejphar.2021.173887

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.

Keywords: Berberine; Cancer stem cell; Chemotherapy; Migration; Ovarian cancer.

MeSH terms

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*
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology
Ovarian Neoplasms / drug therapy*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism
Ovarian Neoplasms / pathology
Polycomb Repressive Complex 1 / genetics
Polycomb Repressive Complex 1 / metabolism
Signal Transduction
Snail Family Transcription Factors / genetics
Snail Family Transcription Factors / metabolism
Vimentin / genetics
Vimentin / metabolism
Zinc Finger Protein GLI1 / genetics
Zinc Finger Protein GLI1 / metabolism*

Substances

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