Huang Qingtian, Yang Jie, Zhang Jiaxing, Yao Leyi, Jiang Baoyi, Du Siyuan, Li Fengjin, Peng Qian, Qin Lingsha, Wang Yanfen, Qi Ling
Institute of Digestive Diseases, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China.
Department of Pathology, the Affiliated Qingyuan Hospital (Qingyuan Peoples's Hospital), Guangzhou Medical University, Qingyuan 511518, Guang Dong, China.
iScience. 2024 Jul 14;27(8):110496. doi: 10.1016/j.isci.2024.110496. eCollection 2024 Aug 16.
Pancreatic cancer is highly lethal with limited effective treatments. This study explores the therapeutic effects of eupalinolide B (EB) from DC on pancreatic cancer cells. Through cellular functional assays, we observed that EB effectively inhibits cell viability, proliferation, migration, and invasion. In a xenograft mouse model, EB treatment resulted in reduced pancreatic cancer tumor growth and decreased expression of Ki-67. Mechanistically, EB induces apoptosis, elevates reactive oxygen species (ROS) levels, and disrupts copper homeostasis. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) identified copper ion binding pathways and potential involvement in cuproptosis. Furthermore, EB enhances the cytotoxic effects of elesclomol (ES), increasing ROS levels in a copper-dependent manner and exhibiting synergistic cytotoxicity. These findings suggest that EB, either alone or in combination with ES, represents a promising strategy for targeting metal ion dysregulation and inducing potential cuproptosis in pancreatic cancer, offering a potential improvement in therapeutic outcomes.
胰腺癌具有高度致死性，有效治疗方法有限。本研究探讨了来自[植物名称未明确，推测为某种植物（DC可能是植物拉丁名缩写）]的榄香醇内酯B（EB）对胰腺癌细胞的治疗效果。通过细胞功能实验，我们观察到EB能有效抑制细胞活力、增殖、迁移和侵袭。在异种移植小鼠模型中，EB治疗导致胰腺癌肿瘤生长减缓，Ki-67表达降低。机制上，EB诱导细胞凋亡，提高活性氧（ROS）水平，并破坏铜稳态。RNA测序（RNA-seq）和基因集富集分析（GSEA）确定了铜离子结合途径以及潜在的铜死亡参与情况。此外，EB增强了依斯氯醇（ES）的细胞毒性作用，以铜依赖的方式增加ROS水平，并表现出协同细胞毒性。这些发现表明，EB单独或与ES联合使用，是针对胰腺癌中金属离子失调和诱导潜在铜死亡的一种有前景的策略，有望改善治疗效果。
