The CBR1 Knockout NCI-H1975 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the CBR1 gene in the human NCI-H1975 lung adenocarcinoma line. This population, generated by target-gene disruption without clonal isolation, provides a loss-of-function model for studying carbonyl reductase 1-dependent pathways. The knockout eliminates CBR1 enzymatic activity, enabling research into drug metabolism and detoxification processes.
NCI-H1975 is a non-small cell lung cancer (NSCLC) epithelial cell line derived from a non-smoker female. It harbors activating EGFR T790M and PIK3CA mutations, which confer tyrosine kinase inhibitor resistance and activate oncogenic signaling. This well-characterized adenocarcinoma model is widely employed in drug sensitivity assays and molecular studies of lung tumor biology.
CBR1 encodes an NADPH-dependent carbonyl reductase that reduces prostaglandins, quinones, and xenobiotics, playing key roles in detoxification and prostaglandin E2 (PGE2) regulation. The enzyme is transcriptionally regulated by NRF2, which dissociates from KEAP1 under oxidative stress and promotes CBR1 expression. CBR1 activity directly reduces PGE2, a lipid mediator involved in inflammation, and interacts with NADPH as a cofactor. By catalyzing carbonyl reduction, CBR1 links arachidonic acid metabolism, xenobiotic detoxification, and cellular responses to oxidative stress.
In the NCI-H1975 context, CBR1 knockout allows dissection of how carbonyl reductase activity influences drug sensitivity and oxidative stress responses. The EGFR T790M mutation drives signaling pathways that may intersect with NRF2-mediated detoxification; thus, CBR1 disruption is expected to alter PGE2 accumulation and ROS levels. This model enables investigation of whether CBR1 loss potentiates or mitigates the effects of carbonyl-generating chemotherapeutics like daunorubicin, providing insight into resistance mechanisms in lung adenocarcinoma.
This polyclonal knockout population supports diverse assays including CBR1 enzyme activity measurement, PGE2 ELISA, cell viability tests with carbonyl-containing chemotherapeutics, and ROS detection. It is suitable for carbonyl reductase inhibitor screening, transcriptomic analysis via RNA-seq, and studies on prostaglandin signaling in the tumor microenvironment. Researchers can employ these cells to explore CBR1-dependent drug metabolism and oxidative stress adaptation. For additional product details, please contact Ascent Research.
