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.

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