The CBR1 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal population of AGS gastric adenocarcinoma cells with targeted disruption of the CBR1 gene. This polyclonal knockout pool provides a heterogeneous model for loss-of-function studies without clonal selection, suitable for pooled drug screening and pathway analysis.
The AGS cell line is a well-characterized model of human gastric adenocarcinoma, widely used in cancer biology to study carcinogenesis, metastasis, and drug resistance. These epithelial cells retain key oncogenic features, making them an appropriate host for CBR1 knockout to examine gastric cancer mechanisms.
CBR1 encodes an NADPH-dependent carbonyl reductase that inactivates prostaglandin E2 (PGE2) by reducing its ??,??-unsaturated carbonyl group, thereby attenuating PGE2-mediated signaling. It also detoxifies reactive aldehydes like 4-hydroxynonenal (4-HNE), protecting cells from oxidative stress. CBR1 expression is transcriptionally regulated by Nrf2 via antioxidant response elements, positioning it downstream of the Nrf2/KEAP1 oxidative stress pathway. The enzyme interacts with NADPH and substrates such as PGE2 and 4-HNE, and its activity intersects with the PTGS2 (COX-2)/PGE2 signaling axis, as well as MAPK/ERK and AKT pathways frequently altered in gastric cancer. CBR1 is a key effector of the Nrf2-mediated antioxidant response, working alongside other Nrf2 targets such as NQO1 to maintain redox balance.
In gastric adenocarcinoma, CBR1 contributes to chemoresistance by metabolizing carbonyl-containing drugs and mitigating oxidative damage. Knockout of CBR1 in AGS cells is expected to increase susceptibility to oxidative stress and reactive carbonyls, potentially enhancing chemosensitivity. This model thus enables dissection of CBR1’s role in drug resistance and redox homeostasis in a gastric cancer context.
This polyclonal knockout product suits a range of applications: drug sensitivity and apoptosis assays to study chemoresistance, ROS detection for oxidative stress profiling, PGE2 ELISA to monitor prostaglandin metabolism, and transcriptomic analyses via RNA-seq. It also supports migration and invasion studies downstream of prostaglandin and steroid signaling, as well as toxicology assays for carbonyl compound evaluation. Additionally, the model facilitates investigations into steroid metabolism, as CBR1 reduces various steroid substrates. Western blotting and RT-qPCR enable knockout confirmation and pathway analysis. For further details, contact Ascent Research.
