Gao Xue, Li Yixiao, Xu Haoran, Ni Shouxiang, Pan Hong, Ma Chunli, Zhao Xiaofei, Zhang Han
Department of Ophthalmology, The Second Hospital of Shandong University, Jinan, China.
Department of Ophthalmology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Med (Lausanne). 2025 Apr 16;12:1554934. doi: 10.3389/fmed.2025.1554934. eCollection 2025.
Retinoblastoma is widely considered the most frequent primary intraocular malignancy during childhood. Xanthatin has been reported to selectively inhibit the proliferation of RB cells, but the underlying mechanism remains uncertain. In this study, human RB cells were treated with different doses of xanthatin, and then cell survival, cell apoptosis, and protein expression were assessed using CCK8 assays, flow cytometry, and western blotting to investigate the possible mechanism of xanthatin in RB cells. A human RB xenograft model was established to demonstrate the effect of xanthatin . Our study shows that xanthatin inhibited cell survival and induced apoptosis in human RB cells. Moreover, xanthatin induced the downregulation of CASP8 and FADD-like apoptosis regulating protein (c-FLIP) and increased the cleavage of caspase-8, caspase-9, caspase-3, and PARP. c-FLIP overexpression impaired xanthatin-induced apoptosis. Furthermore, NAC, which can reduce xanthatin-triggered Reactive oxygen species (ROS), alleviated xanthin-induced apoptosis and c-FLIP downregulation. , analysis confirmed that xanthatin was an efficacious drug against xenograft tumors. Xanthatin induced apoptosis of the human RB cells both and through ROS-mediated c-FLIP inhibition. Our research provides important mechanistic insight into potential cancer treatments with ROS/c-FLIP axis in xanthatin-induced apoptosis and makes them candidates for developing new directed therapies.
视网膜母细胞瘤被广泛认为是儿童期最常见的原发性眼内恶性肿瘤。据报道，山柑子萜醇可选择性抑制视网膜母细胞瘤（RB）细胞的增殖，但其潜在机制仍不确定。在本研究中，用不同剂量的山柑子萜醇处理人RB细胞，然后使用CCK8检测、流式细胞术和蛋白质印迹法评估细胞存活、细胞凋亡和蛋白质表达，以研究山柑子萜醇在RB细胞中的可能机制。建立人RB异种移植模型以证明山柑子萜醇的作用。我们的研究表明，山柑子萜醇抑制人RB细胞的存活并诱导其凋亡。此外，山柑子萜醇诱导半胱天冬酶8（CASP8）和FADD样凋亡调节蛋白（c-FLIP）下调，并增加半胱天冬酶-8、半胱天冬酶-9、半胱天冬酶-3和聚（ADP-核糖）聚合酶（PARP）的裂解。c-FLIP过表达削弱了山柑子萜醇诱导的凋亡。此外，能够减少山柑子萜醇引发的活性氧（ROS）的N-乙酰半胱氨酸（NAC）减轻了山柑子萜醇诱导的凋亡和c-FLIP下调。分析证实，山柑子萜醇是一种对异种移植肿瘤有效的药物。山柑子萜醇通过ROS介导的c-FLIP抑制在体外和体内诱导人RB细胞凋亡。我们的研究为山柑子萜醇诱导凋亡中ROS/c-FLIP轴潜在的癌症治疗提供了重要的机制见解，并使其成为开发新的定向疗法的候选药物。
