Pancreatic cancer is a refractory cancer with limited treatment options. Various cancer types are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Eugenol, the main component of clove oil, exhibits anticancer, anti-inflammatory, and antioxidant effects. However, no studies have reported that eugenol increases TRAIL sensitivity by upregulating death receptor (DR) expression. Here, we aimed to investigate eugenol as a potent TRAIL sensitizer. Increased apoptosis and inhibition of cell proliferation was observed in pancreatic cancer cells treated with eugenol and TRAIL compared with those treated with eugenol alone. Eugenol upregulated the expression of DR5, inhibited the FLICE-inhibitory protein (FLIP), an anti-apoptotic protein, and increased p53, a tumor suppressor protein. In addition, eugenol induced the generation of reactive oxygen species (ROS) and caused endoplasmic reticulum (ER) stress. C/EBP-homologous protein (CHOP) knockdown using siRNA decreased the expression of DR5 and reduced the combined effects of eugenol and TRAIL. These results demonstrate that eugenol enhances TRAIL-induced apoptosis by upregulating DR5 through the ROS-mediated ER stress–CHOP pathway, which enhances ER stress by inducing p53 and downregulating FLIP expression. This suggests that eugenol has the potential to treat pancreatic cancer by increasing cell sensitivity to TRAIL.
胰腺癌是一种难治性癌症，治疗选择有限。多种癌症类型对肿瘤坏死因子相关凋亡诱导配体（TRAIL）具有耐药性。丁香油主要成分丁香酚具有抗癌、抗炎和抗氧化作用。然而，尚无研究报道丁香酚通过上调死亡受体（DR）表达来增强TRAIL敏感性。本研究旨在探讨丁香酚作为TRAIL增敏剂的作用机制。与单独使用丁香酚处理相比，联合使用丁香酚与TRAIL处理的胰腺癌细胞表现出凋亡增加和细胞增殖抑制。丁香酚可上调DR5表达，抑制抗凋亡蛋白FLICE抑制蛋白（FLIP），并增加肿瘤抑制蛋白p53的表达。此外，丁香酚诱导活性氧（ROS）生成并引发内质网（ER）应激。使用siRNA敲低C/EBP同源蛋白（CHOP）可降低DR5表达，并减弱丁香酚与TRAIL的联合效应。这些结果表明，丁香酚通过ROS介导的内质网应激-CHOP通路上调DR5表达，该通路通过诱导p53和下调FLIP表达增强内质网应激，从而增强TRAIL诱导的细胞凋亡。这表明丁香酚可能通过提高细胞对TRAIL的敏感性来治疗胰腺癌。
肿瘤(癌症)患者之家