小檗碱通过 GLI1 抑制化疗加重的卵巢癌干细胞样特征和转移。
Berberine inhibits chemotherapy-exacerbated ovarian cancer stem cell-like characteristics and metastasis through GLI1.
机构信息
Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun 130021, People's Republic of China.
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.
出版信息
Eur J Pharmacol. 2021 Mar 15;895:173887. doi: 10.1016/j.ejphar.2021.173887. Epub 2021 Jan 20.
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.
尽管在卵巢癌治疗中取得了显著的临床疗效，但转移率高仍然是影响预后的一个障碍。本研究旨在探讨小檗碱在抑制化疗加重的卵巢癌转移中的作用。我们发现，化疗通过转录因子 GLI1 加剧迁移和癌症干细胞（CSC）样特征，调节多能相关基因 BMI1 和上皮-间充质转化（EMT）标志物波形蛋白和 SNAIL。小檗碱不仅可以下调 CSC 样特征，还可以通过抑制化疗激活的 GLI1/BMI1 信号通路来逆转 EMT 和迁移。总之，我们的研究揭示了小檗碱在克服化疗加重的卵巢癌转移中的关键作用，为联合化疗预防卵巢癌化疗期间转移提供了一种潜在的辅助治疗药物。
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