Cepharanthine sensitizes gastric cancer cells to chemotherapy by targeting TRIB3-FOXO3-FOXM1 axis to inhibit autophagy

作者：Yangyang Lu, Yuanyuan Fang, Shasha Wang, Jing Guo, Jialin Song, Liang Zhu, Zhong-Kun Lin, Rui Wang, Siyi Zhang, Wensheng Qiu, Wei-wei Qi · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.156161 · 被引用次数：22 · 研究领域：Autophagy in Disease and Therapy、FOXO transcription factor regulation、Berberine and alkaloids research

BACKGROUND: Gastric cancer is among the common solid tumors. Chemotherapy resistance is the most common issue in gastric cancer treatment. Inhibiting intracellular autophagy may be a feasible method for overcoming chemotherapy resistance. Cepharanthine (CEP), a natural small molecule extracted from the stephania cephalantha Hayata plant, has been demonstrated to significantly inhibit cancer growth and can regulate autophagy. Although CEP can significantly inhibit cancer growth, it remains unclear whether CEP can regulate autophagy in gastric cancer. This study aimed to investigate whether CEP can enhance the sensitivity of gastric cancer to chemotherapy and elucidate its molecular mechanism. METHODS: Three gastric cancer cell lines (AGS, SGC7901, and MFC) and one normal gastric mucosal epithelial cell line (GES-1) were used for in vitro experiments. The characterization of autophagy in gastric cancer cells included the detection of autophagy markers and autophagy flux through immunofluorescence staining and Western blotting, as well as the assessment of lysosomal function using fluorescence staining (LysoTracker Red DND-99, Acridine Orange staining) and Western blotting. The cytotoxicity of CEP, autophagy inhibitors (chloroquine [CQ] and 3-methyladenine [3MA]), and chemotherapy drugs (doxorubicin [DOX] and cisplatin [CIS]) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell colony formation, and fluorescence staining techniques (H2...