文章標題: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
發表時間:2026-4-24
DOI:10.1038/s41598-026-49458-3
文獻主題: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.

文章標題:Salinomycin通過阻斷內體酸化抑制體內外正痘病毒感染
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
發表時間:2026-4-24
DOI:10.1038/s41598-026-49458-3
文獻主題:摘要
肝內膽管細胞癌(ICC)是一種高度侵襲性的肝臟惡性腫瘤,其全球發病率上升且預后不佳。盡管最近治療策略有所進展,但ICC的有效治療選擇仍然有限。Solamargine(SM)是一種天然類固醇生物堿,已經顯示出抗癌活性,但其在ICC中的機制尚未wan全明確。本研究表明,SM通過在體外和體內誘導凋亡和鐵死亡抑制ICC的進展。SM顯著抑制ICC細胞(HUCCT-1和HCCC-9810)的增殖、遷移和侵襲,同時對正常膽道上皮細胞(HIBEC)的細胞毒性極低。在機制方面,SM誘導線粒體功能障礙、ROS積累和脂質過氧化,從而導致凋亡和鐵死亡。轉錄組測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的通路,包括MAPK信號通路。蛋白印跡分析和藥理抑制實驗證實p38 MAPK激活對SM誘導的細胞死亡至關重要,ROS作為上游激活因子。在體內,SM顯著抑制了原位和皮下ICC小鼠模型的腫瘤生長,并顯示出比吉西他濱更好的耐受性。腫瘤組織分析進一步證實了凋亡和鐵死亡標志物增加以及p38 MAPK的激活。這些發現表明,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相關,并可能涉及ROS/p38 MAPK信號軸,突顯其作為ICC潛在治療候選藥物的價值。
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