Photodynamic therapy inhibits cancer progression and induces ferroptosis and apoptosis by targeting P53/GPX4/SLC7A11 signaling pathways in cholangiocarcinoma

作者：Xiaodong Yan, Zhongmin Li, Huaiyu Chen, Yang Fu, Qing Tian, Yamin Zhang · 发表于：Photodiagnosis and Photodynamic Therapy · 年份：2024 · DOI：10.1016/j.pdpdt.2024.104104 · 被引用次数：17 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Photodynamic Therapy Research Studies、Ferroptosis and cancer prognosis

• HiPorfin-mediated PDT enhances apoptosis of cholangiocarcinoma cells. • HiPorfin-mediated PDT blocks the GSH synthesis-related pathways to active P53/SLC7A11/GPX4 signaling pathway. • HiPorfin-mediated PDT inhibited xenograft tumors in vivo through the combined effect of apoptosis and ferroptosis. Cholangiocarcinoma (CCA) is a malignant tumor with a poor prognosis. The specific mechanism of photodynamic therapy (PDT) in treating CCA remains unclear. This study aims to investigate the mechanisms of PDT in the treatment of CCA and try to improve the therapeutic effect of PDT by intervening associated signaling pathways. The Cell Counting Kit-8 (CCK-8) was used to examine the cytotoxicity of CCA cell lines following PDT. Apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. A transmission electron microscope was used to study the changes in cell mitochondria after PDT. The levels of glutathione (GSH), malondialdehyde (MDA), ferrous iron (Fe 2+ ), lactate dehydrogenase (LDH), and lipid peroxide (LPO) were determined. Changes in the expression of apoptosis and ferroptosis-related proteins were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Xenograft tumor models were developed to investigate the effects of PDT on tumor proliferation, apoptosis, and ferroptosis in vivo. PDT inhibited tumor proliferation and induced apoptosis both in vivo and in vitro. This treatment led to swelling and damage of the ...