文章标题：Salinomycin inhibits orthopoxvirus infection in vitro and 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 and 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 not fully understood. This study shows that SM inhibits ICC progression by inducing both apoptosis and ferroptosis in vitro and in vivo. SM significantly suppressed proliferation, migration, and invasion of ICC cells (HUCCT-1 and HCCC-9810), with minimal cytotoxicity toward normal biliary epithelial cells (HIBEC). Mechanistically, SM induced mitochondrial dysfunction, ROS accumulation, and lipid peroxidation, leading to apoptosis and ferroptosis. Transcriptome sequencing and gene set enrichment analysis (GSEA) revealed that SM treatment activated apoptosis- and ferroptosis-related pathways, including MAPK signaling. Western blot analysis and 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 and subcutaneous ICC mouse models and showed better tolerability than gemcitabine. Tumor tissue analysis further confirmed increased markers of apoptosis and 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 and ferroptosis and may involve the ROS/p38 MAPK signaling axis, highlighting its potential as a therapeutic candidate for ICC.
文章标题：Salinomycin通过阻断内体酸化抑制体内外正痘病毒感染
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：摘要
肝内胆管细胞癌（ICC）是一种高度侵袭性的肝脏恶性肿瘤，其全球发病率上升且预后不佳。尽管最近治疗策略有所进展，但ICC的有效治疗选择仍然有限。Solamargine（SM）是一种天然类固醇生物碱，已经显示出抗癌活性，但其在ICC中的机制尚未wan全明确。本研究表明，SM通过在体外和体内诱导凋亡和铁死亡抑制ICC的进展。SM显著抑制ICC细胞（HUCCT-1和HCCC-9810）的增殖、迁移和侵袭，同时对正常胆道上皮细胞（HIBEC）的细胞毒性极低。在机制方面，SM诱导线粒体功能障碍、ROS积累和脂质过氧化，从而导致凋亡和铁死亡。转录组测序和基因集富集分析（GSEA）显示，SM处理激活了与凋亡和铁死亡相关的通路，包括MAPK信号通路。蛋白印迹分析和药理抑制实验证实p38 MAPK激活对SM诱导的细胞死亡至关重要，ROS作为上游激活因子。在体内，SM显著抑制了原位和皮下ICC小鼠模型的肿瘤生长，并显示出比吉西他滨更好的耐受性。肿瘤组织分析进一步证实了凋亡和铁死亡标志物增加以及p38 MAPK的激活。这些发现表明，SM在ICC中具有双重抗肿瘤作用，这可能与凋亡和铁死亡的诱导相关，并可能涉及ROS/p38 MAPK信号轴，突显其作为ICC潜在治疗候选药物的价值。
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