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Updated: Apr 23, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Photodynamic therapy induces pyroptosis via GSDMD pathway in NCI-H226 human lung squamous carcinoma cells
Qi-Zi Huang1, Yi-Wei Cao1, Lin-Sen Yu1
1Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Abstract:
Photodynamic therapy (PDT) is a promising minimally invasive anticancer strategy with high tumor-targeting specificity, attracting considerable attention in oncology. Pyroptosis, a pro-inflammatory programmed cell death (PCD) mediated by the gasdermin (GSDM) family, is tightly regulated by the gasdermin D (GSDMD)-dependent pathway and contributes to tumor regulation. However, the molecular mechanism of PDT-induced pyroptosis in lung squamous cell carcinoma (LUSC) NCI-H226 cells remains unclear. Herein, we demonstrated that PDT effectively triggers GSDMD-mediated pyroptosis in NCI-H226 cells, with typical morphological features including cytoplasmic bubble formation, membrane rupture, intracellular content release and pro-inflammatory mediator secretion. Mechanistically, PDT-induced pyroptosis involves NLRP3 inflammasome upregulation, caspase-1 activation and GSDMD cleavage to generate GSDMD-N, key events driving pyroptosis. PDT treatment significantly enhanced lactate dehydrogenase (LDH) release and secretion of pro-inflammatory cytokines including IL-1β and IL-18. Notably, GSDMD silencing or caspase-1 inhibition with VX765 markedly abrogated PDT-induced pyroptosis. Collectively, PDT induces pyroptosis in NCI-H226 cells via the NLRP3-caspase-1-GSDMD axis. This study reveals a novel anti-tumor mechanism of PDT in LUSC, providing a theoretical basis and potential therapeutic targets for clinical LUSC management.
Insights
Photodynamic therapy (PDT) triggers gasdermin D (GSDMD)-mediated pyroptosis in lung cancer cells. This programmed cell death mechanism offers a novel anti-tumor strategy for lung squamous cell carcinoma (LUSC) management.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Photodynamic therapy (PDT) is an emerging anticancer treatment with high tumor specificity.
- Pyroptosis, a programmed cell death pathway involving gasdermin proteins, plays a role in tumor regulation.
- The precise mechanism of PDT-induced pyroptosis in lung squamous cell carcinoma (LUSC) NCI-H226 cells was previously undefined.
Purpose of the Study:
- To elucidate the molecular mechanism of PDT-induced pyroptosis in NCI-H226 cells.
- To investigate the role of the NLRP3 inflammasome, caspase-1, and gasdermin D (GSDMD) in PDT-induced pyroptosis.
- To explore the potential of PDT as a therapeutic strategy for LUSC.
Main Methods:
- NCI-H226 cells were treated with PDT.
- Morphological changes indicative of pyroptosis were observed.
- Levels of lactate dehydrogenase (LDH), IL-1β, and IL-18 were measured.
- GSDMD silencing and caspase-1 inhibition (VX765) were employed to assess their impact on pyroptosis.
Main Results:
- PDT effectively induced pyroptosis in NCI-H226 cells, characterized by membrane rupture and release of cellular contents.
- PDT treatment led to NLRP3 inflammasome upregulation, caspase-1 activation, and GSDMD cleavage.
- PDT significantly increased LDH release and secretion of IL-1β and IL-18.
- GSDMD silencing or caspase-1 inhibition suppressed PDT-induced pyroptosis.
Conclusions:
- PDT induces pyroptosis in NCI-H226 cells through the NLRP3-caspase-1-GSDMD pathway.
- This study reveals a novel anti-tumor mechanism for PDT in LUSC.
- The findings provide a theoretical basis and potential therapeutic targets for LUSC treatment.
