# Mechanistic insights into 125I seed implantation therapy for Cholangiocarcinoma: focus on ROS-Mediated apoptosis and the role of GPX2

## TL;DR

This study explores how 125I seed implantation therapy fights cholangiocarcinoma by increasing reactive oxygen species and reducing GPX2, leading to cancer cell death.

## Contribution

The study reveals the role of ROS-mediated apoptosis and GPX2 downregulation in 125I seed therapy for cholangiocarcinoma.

## Key findings

- 125I seeds inhibited tumor growth and induced apoptosis in cholangiocarcinoma cells.
- Treatment increased ROS levels, suggesting ROS-mediated apoptosis as a key mechanism.
- GPX2 downregulation was observed, potentially enhancing ROS accumulation and cell death.

## Abstract

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).

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.

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.

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.