The CASP7 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the CASP7 gene has been disrupted to eliminate functional caspase-7 expression. This product provides a heterogeneous mixture of cells with targeted gene modifications, avoiding clonal artifacts and enabling population-level analyses. It serves as a reliable loss-of-function model for investigating apoptotic signaling networks within a lung adenocarcinoma context.
The NCI-H1975 host cell line was derived from a female patient with non-small cell lung adenocarcinoma and carries EGFR T790M and p53 mutations. These epithelial cells display uncontrolled proliferation and metastatic potential, and are widely employed to study resistance to EGFR tyrosine kinase inhibitors. The p53 deficiency compromises DNA damage-induced apoptosis, rendering the line highly relevant for examining how additional apoptotic defects, such as CASP7 knockout, contribute to therapy resistance and tumor progression.
Caspase-7 is an executioner caspase activated by caspase-8 and -9 downstream of death receptors (Fas, TRAIL-R) and the mitochondrial apoptosome. It cleaves substrates such as PARP, lamin A/C, and DFF45/ICAD to trigger DNA fragmentation and cell death. Key regulators include XIAP and SMAC/DIABLO, and cross-talk with the NLRP3 inflammasome extends its roles. Upon DNA damage, p53-driven Bax/Bak pore formation releases cytochrome c, forming the Apaf-1/caspase-9 complex that proteolytically activates caspase-7.
Disrupting CASP7 in NCI-H1975 cells abrogates a critical executioner step within both intrinsic and extrinsic apoptotic cascades, allowing evasion of programmed cell death. This mimics the apoptosis deficiency observed in drug-resistant lung adenocarcinomas, where reduced caspase activity limits the efficacy of agents such as cisplatin, paclitaxel, and EGFR inhibitors. The cooperative presence of EGFR T790M and p53 mutations heightens the model’s relevance for studying how proliferation signaling and apoptosis suppression synergize to promote tumorigenicity and metastasis.
This polyclonal knockout population supports diverse experimental strategies: western blotting for caspase-7 and its substrates, annexin V flow cytometry for apoptosis quantification, and TUNEL assays for DNA fragmentation. It enables drug screening for caspase-independent death inducers, colony formation studies of oncogenic potential, and xenograft tumor growth assays. Additionally, RT-qPCR profiling of apoptotic genes and caspase activity measurements can confirm functional knockout and downstream effects. For further information, contact Ascent Research.
