Photodynamic Therapy Induces Colorectal Cancer Cell Death via GSDME-Dependent Pyroptosis Pathway

This study aimed to investigate whether photodynamic therapy (PDT) promotes colorectal cancer cell death through the gasdermin E (GSDME)-dependent pyroptosis pathway. Colon cancer cells with high (SW480) or low (RKO) GSDME expression were treated with PDT. Cell viability and morphology were analyzed via flow cytometry, microscopy, and transmission electron microscopy. Western blot and ELISA were used to detect pyroptosis-related proteins (cleaved caspase-3/7 and GSDME) and inflammatory cytokines (IL-1β/IL-18). PDT markedly increased death in GSDME-high SW480 cells, accompanied by pyroptotic hallmarks (cell swelling, membrane rupture, cytoplasmic leakage), upregulated cleaved caspase-3/7 and GSDME proteins, and significantly elevated inflammatory cytokine secretion. In contrast, GSDME-low RKO cells showed minimal pyroptotic markers but activated caspase-3/7, suggesting apoptosis as the predominant death mode. PDT induces colorectal cancer cell death via GSDME-dependent pyroptosis, with efficacy dependent on GSDME expression levels. Enhancing GSDME targeting may improve PDT outcomes, providing a novel approach for therapeutic optimization.