上睑下垂
光动力疗法
癌症研究
巴基斯坦卢比
程序性细胞死亡
细胞凋亡
化学
生物
糖酵解
丙酮酸激酶
生物化学
酶
有机化学
作者
Lisha Li,Dongfeng Song,Ling Qi,Mingxia Jiang,Yiming Wu,Junqing Gan,Kui Cao,Yanjing Li,Yuxian Bai,Tongsen Zheng
标识
DOI:10.1016/j.canlet.2021.07.014
摘要
Photodynamic therapy (PDT) uses a photosensitizer (PS) and visible light to induce cancer cell death. Pyroptosis is a new type of programmed cell death that is associated with the gasdermin protein family. However, the precise mechanism of pyroptosis in PDT-induced suppression of esophageal cancer remains unknown. We demonstrate that PDT can induce gasdermin E (GSDME)-mediated pyroptosis, which is characterized by the formation of pyroptotic blebs in esophageal squamous cell carcinoma (ESCC), which burst and release intracellular contents and pro-inflammatory mediators. Mechanistically, PDT may inhibit pyruvate kinase M2 (PKM2) and consequently, activate caspase-8 and caspase-3, which ultimately releases N-GSDME and triggers pyroptosis in ESCC. Moreover, PDT decreased the efficiency of pyroptosis in the presence of a glycolytic inhibitor. Overall, our results show that PDT induces pyroptosis in ESCC by targeting the PKM2/caspase-8/caspase-3/GSDME axis. This is the first in-depth study of the specific mechanism underlying PKM2-mediated pyroptosis under PDT in ESCC, and potentially has great implications for the clinical application of PDT in ESCC.
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