European journal of pharmacology · 2021
Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1.
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Zhao Yawei, Yang Xuehan, Zhao Jingtong, Gao Mohan, Zhang Min, Shi Tongfei, Zhang Fan, Zheng Xiao, Pan Yue, Shao Dan, Li Jing, He Kan, Chen Li
Аннотация
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.
Предметные рубрики MeSH
Antineoplastic AgentsBerberineCarboplatinCell Line, TumorCell MovementCoculture TechniquesEpithelial-Mesenchymal TransitionEtoposideFemaleGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisNeoplastic Stem CellsOvarian NeoplasmsPolycomb Repressive Complex 1Signal TransductionSnail Family Transcription FactorsVimentinZinc Finger Protein GLI1