Mechanistic insights into 125I seed implantation therapy for Cholangiocarcinoma: focus on ROS-Mediated apoptosis and the role of GPX2
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Published:2024-06-25
Issue:6
Volume:150
Page:
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ISSN:1432-1335
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Container-title:Journal of Cancer Research and Clinical Oncology
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language:en
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Short-container-title:J Cancer Res Clin Oncol
Author:
Luo Jun,Yao Zheng,Liang Weiren,Song Danjun,Zeng Hui,Jiang Yi,Bao Zhehan,Zheng Jiaping,Ding Yinan
Abstract
Abstract
Objectives
Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of 125I seed implantation therapy in CCA, focusing on the induction of reactive oxygen species (ROS)-mediated apoptosis and the involvement of glutathione peroxidase 2 (GPX2).
Materials and 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.
Conclusion
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.
Funder
Zhejiang Medical and Health Science and Technology Program China Postdoctoral Science Foundation
Publisher
Springer Science and Business Media LLC
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