The GSDMD Knockout NCI-H1299 Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population for the gasdermin D (GSDMD) gene in the human non-small cell lung carcinoma (NSCLC) line NCI-H1299. This polyclonal pool provides a heterogeneous gene-disrupted model suitable for population-level loss-of-function studies without clonal isolation.
The NCI-H1299 cell line originates from a lymph node metastasis of lung adenocarcinoma and serves as a widely used in vitro model for NSCLC metastasis. These adherent epithelial cells harbor a p53 deficiency, which supports their transformed and metastatic characteristics, enabling investigation of tumor progression and therapy resistance mechanisms.
GSDMD acts as the executioner of pyroptosis, a pro-inflammatory programmed cell death. Inflammasome activation triggers caspase-1, caspase-4, or caspase-5 to cleave GSDMD, removing its autoinhibitory C-terminal domain. The liberated N-terminal fragment then oligomerizes, forming membrane pores that cause cell swelling, lysis, and release of IL-1??, IL-18, and DAMPs. Upstream, NLRP3 and AIM2 inflammasomes recruit ASC to activate caspase-1, while cytosolic LPS activates caspase-4/5. NF-??B transcriptionally primes NLRP3 and pro-IL-1?? expression.
This knockout model enables dissection of pyroptosis in p53-deficient NSCLC. GSDMD loss allows researchers to study how pyroptotic signaling affects metastatic behavior, apoptotic sensitivity, and immune interactions in lung cancer. It also facilitates exploration of GSDMD-independent cytokine release and alternative cell death pathways, providing insights into compensatory mechanisms. Emerging data suggest pyroptosis can exert both anti-tumor and pro-tumor effects, making this model valuable for investigating context-dependent roles of inflammatory cell death.
Applications include mechanistic pyroptosis research, inflammasome signaling studies, and screening for pyroptosis modulators. Researchers can employ western blotting for GSDMD cleavage, LDH release assays, ELISA for IL-1??/IL-18, caspase-1 activity measurements, immunofluorescence for pore formation, flow cytometry, and morphological imaging. The polyclonal knockout pool is also suited for co-culture systems examining pyroptosis-driven immune responses. For further information, please contact Ascent Research.
