文章标题：Salinomycin inhibits orthopoxvirus infection in vitro in vivo by blocking endosomal acidification

作者列表：Wang Xiang, Luo Kai, Bai He, Zhang Xudong, Qu Jialin, Wang Xiaoqing, Sun Xu, Zhao Yuting, Wang Bin, Zhang Guixin

影响因子：3.9

期刊：Scientific Reports

发表时间：2026－4－24

DOI:10.1038/s41598－026－49458－3

文献主题：Abstract

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with rising global incidence poor prognosis. Despite recent advances in treatment strategies, effective therapeutic options for ICC remain limited. Solamargine (SM), a natural steroidal alkaloid, has demonstrated anticancer activity, yet its mechanisms in ICC are fully understood. This study shows that SM inhibits ICC progression by inducing both apoptosis ferroptosis in vitro in vivo. SM significantly suppressed proliferation, migration, invasion of ICC cells (HUCCT－1 HCCC－9810), with minimal cytotoxicity toward normal biliary epithelial cells (HIBEC). Mechanistically, SM induced mitochondrial dysfunction, ROS accumulation, lipid peroxidation, leading to apoptosis ferroptosis. Tranｓcriptome sequencing gene set enrichment analysis (GSEA) revealed that SM treatment activated apoptosis－ ferroptosis－related pathways, including MAPK signaling. Western blot analysis pharmacological inhibition assays confirmed that p38 MAPK activation was essential for SM－induced cell death, with ROS acting as an upstream activator. In vivo, SM significantly inhibited tumor growth in both orthotopic subcutaneous ICC mouse models showed better tolerability than gemcitabine. Tumor tissue analysis further confirmed increased markers of apoptosis ferroptosis, along with p38 MAPK activation. These findings suggest that SM exerts dual antitumor effects in ICC, which are associated with the induction of apoptosis ferroptosis may involve the ROS/p38 MAPK signaling axis, highlighting its potential as a therapeutic cidate for ICC.