The CBR3 Knockout NCI-H1975 Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the CBR3 gene in a human lung adenocarcinoma host. This heterogeneous pool originates from transient transfection of Cas9 and guide RNA complexes, yielding a mixture of loss-of-function alleles across the cell population without single-cell cloning. The polyclonal format captures genetic diversity and circumvents clonal artifacts, making it suitable for bulk assays that require representation of edited genotypes. By providing a ready-to-use disrupted population, the product facilitates streamlined functional genomics investigations without the delays of clone isolation.
The parental NCI-H1975 line is a well-characterized model of non-small cell lung cancer (NSCLC), derived from a female patient with lung adenocarcinoma. These epithelial cells display hallmark features of adenocarcinoma, including mutations in key oncogenic drivers and tumor suppressors, and are routinely employed to study NSCLC biology, therapeutic response, and resistance mechanisms. The integration of CBR3 knockout into this genetic background preserves the native signaling and metabolic context, enabling precise interrogation of carbonyl reductase function within clinically relevant lung adenocarcinoma settings.
CBR3 encodes carbonyl reductase 3, a monomeric NADPH-dependent enzyme that reduces carbonyl-containing xenobiotics and endogenous compounds. Activated by NRF2 under oxidative stress or electrophilic stimuli, CBR3 forms a detoxification axis with NQO1 and AKR1C family members. It employs NADPH to convert substrates such as the anthracycline doxorubicin into less active metabolites. This enzymatic activity alters intracellular drug availability and redox homeostasis, positioning CBR3 at a critical junction between antioxidant defense and drug metabolism.
In NCI-H1975 lung adenocarcinoma, CBR3 knockout provides a clean background to investigate its role in drug metabolism and chemoresistance. Ablating CBR3 permits direct assessment of doxorubicin sensitivity, as increased activity correlates with anthracycline inactivation. The polyclonal model supports population-level analyses of viability, apoptosis, and metabolic flux, capturing response heterogeneity while retaining native NSCLC signaling. This system is ideal for exploring how NRF2-driven detoxification pathways contribute to therapeutic evasion.
This knockout product supports a range of experimental workflows, including drug sensitivity assays (e.g., MTT and colony formation), carbonyl reductase activity measurements, western blotting, RT-qPCR, and transcriptomic profiling by RNA-seq. The polyclonal format is well-suited for comparative studies between wild-type and CBR3-disrupted populations in signaling, metabolism, and pharmacology research. By providing a reliable loss-of-function resource, the model accelerates investigations into lung adenocarcinoma biology and chemoresistance. For further details or ordering, please contact Ascent Research.
