文章標(biāo)題：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
影響因子：3.9
期刊：Scientific Reports
發(fā)表時(shí)間：2026-4-24
DOI:10.1038/s41598-026-49458-3
文獻(xiàn)主題：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.
文章標(biāo)題：Salinomycin通過(guò)阻斷內(nèi)體酸化抑制體內(nèi)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
影響因子：3.9
期刊：Scientific Reports
發(fā)表時(shí)間：2026-4-24
DOI:10.1038/s41598-026-49458-3
文獻(xiàn)主題：摘要
肝內(nèi)膽管細(xì)胞癌（ICC）是一種高度侵襲性的肝臟惡性腫瘤，其全球發(fā)病率上升且預(yù)后不佳。盡管最近治療策略有所進(jìn)展，但I(xiàn)CC的有效治療選擇仍然有限。Solamargine（SM）是一種天然類固醇生物堿，已經(jīng)顯示出抗癌活性，但其在ICC中的機(jī)制尚未wan全明確。本研究表明，SM通過(guò)在體外和體內(nèi)誘導(dǎo)凋亡和鐵死亡抑制ICC的進(jìn)展。SM顯著抑制ICC細(xì)胞（HUCCT-1和HCCC-9810）的增殖、遷移和侵襲，同時(shí)對(duì)正常膽道上皮細(xì)胞（HIBEC）的細(xì)胞毒性極低。在機(jī)制方面，SM誘導(dǎo)線粒體功能障礙、ROS積累和脂質(zhì)過(guò)氧化，從而導(dǎo)致凋亡和鐵死亡。轉(zhuǎn)錄組測(cè)序和基因集富集分析（GSEA）顯示，SM處理激活了與凋亡和鐵死亡相關(guān)的通路，包括MAPK信號(hào)通路。蛋白印跡分析和藥理抑制實(shí)驗(yàn)證實(shí)p38 MAPK激活對(duì)SM誘導(dǎo)的細(xì)胞死亡至關(guān)重要，ROS作為上游激活因子。在體內(nèi)，SM顯著抑制了原位和皮下ICC小鼠模型的腫瘤生長(zhǎng)，并顯示出比吉西他濱更好的耐受性。腫瘤組織分析進(jìn)一步證實(shí)了凋亡和鐵死亡標(biāo)志物增加以及p38 MAPK的激活。這些發(fā)現(xiàn)表明，SM在ICC中具有雙重抗腫瘤作用，這可能與凋亡和鐵死亡的誘導(dǎo)相關(guān)，并可能涉及ROS/p38 MAPK信號(hào)軸，突顯其作為ICC潛在治療候選藥物的價(jià)值。
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