METHODS: Human cholangiocarcinoma cell lines QBC939 and RBE were purchased for in vitro studies. In vivo studies were performed using a rabbit VX2 CCA model. Apoptosis and proliferation were detected by TUNEL staining and clone formation, respectively. ROS generation was detected by dihydroethidium staining. Histological evaluation was performed by hematoxylin and eosin staining. Protein expression was determined by Western blotting and immunohistochemistry.
RESULTS: Our results demonstrate that 125I seeds effectively inhibited tumor growth in the rabbit VX2 tumor model and promoted the apoptosis of CCA cells in vitro in a dose-dependent manner. Molecular analyses indicate a marked increase in reactive oxygen species (ROS) levels following treatment with 125I seeds, suggesting the involvement of ROS-mediated apoptosis in the therapeutic mechanism. Furthermore, the downregulation of glutathione peroxidase 2 (GPX2) was observed, indicating its potential role in modulating ROS-mediated apoptosis in CCA.
CONCLUSIONS: 125I seed implantation therapy exerts therapeutic effects on CCA by inducing ROS-mediated apoptosis. The downregulation of GPX2 may contribute to enhanced ROS accumulation and apoptotic cell death. These findings provide mechanistic insights into the therapeutic potential of 125I seed implantation for CCA and highlight ROS-mediated apoptosis and GPX2 regulation as promising targets for further investigation and therapeutic intervention in this malignancy.
方法:购买人胆管癌细胞系QBC939和RBE用于体外研究。使用兔VX2CCA模型进行体内研究。通过TUNEL染色和克隆形成检测细胞凋亡和增殖,分别。通过二氢乙锭染色检测ROS的产生。通过苏木精和伊红染色进行组织学评估。通过蛋白质印迹和免疫组织化学确定蛋白质表达。
结果:我们的结果表明,125I种子在兔VX2肿瘤模型中有效抑制肿瘤生长,并以剂量依赖的方式促进CCA细胞的凋亡。分子分析表明,用125I种子处理后,活性氧(ROS)水平显着增加。提示ROS介导的细胞凋亡参与治疗机制。此外,观察到谷胱甘肽过氧化物酶2(GPX2)的下调,表明其在调节CCA中ROS介导的凋亡中的潜在作用。
结论:125I粒子植入疗法通过诱导ROS介导的细胞凋亡对CCA具有治疗作用。GPX2的下调可能有助于增强的ROS积累和凋亡性细胞死亡。这些发现为125I种子植入对CCA的治疗潜力提供了机制上的见解,并强调了ROS介导的细胞凋亡和GPX2调节是该恶性肿瘤进一步研究和治疗干预的有希望的靶标。