The CBR4 Knockout AGS Polyclonal Cells consist of a heterogeneous population of AGS gastric epithelial cells engineered with CRISPR/Cas9 to disrupt the CBR4 gene. This polyclonal knockout pool serves as a loss-of-function model for carbonyl reductase 4, enabling researchers to interrogate its role in detoxification pathways without clonal artifacts. The ablation of CBR4 eliminates NADPH-dependent carbonyl reductase activity, providing a cellular system to study redox regulation and xenobiotic metabolism in a gastric cancer context.
The AGS cell line is derived from a human gastric adenocarcinoma and is extensively used to investigate gastric cancer biology, Helicobacter pylori infection, and epithelial-mesenchymal transition (EMT). As a gastric epithelial model, AGS cells retain key signaling properties of the gastric mucosa, making them particularly valuable for examining oxidative stress responses and carcinogen metabolism. The polyclonal knockout format maintains the inherent genetic variability of the host cells, ensuring broad applicability while consistently abolishing CBR4 function.
CBR4 encodes an NADPH-dependent carbonyl reductase belonging to the short-chain dehydrogenase/reductase (SDR) family. It catalyzes the reduction of endogenous and xenobiotic carbonyl compounds, such as toxic quinones and prostaglandins, thereby contributing to cellular detoxification and redox homeostasis. The gene is transcriptionally activated by NFE2L2 (NRF2) and the aryl hydrocarbon receptor (AHR) in response to oxidative stress stimuli. Downstream, CBR4??s activity interfaces with the NRF2?CKEAP1?CNQO1 antioxidant pathway and AHR?CCYP1A1-mediated metabolism. Its knockout disrupts this protective network, impairing the conversion of reactive electrophiles and potentially sensitizing cells to oxidative damage.
In the context of AGS gastric adenocarcinoma cells, CBR4 loss impedes the reduction of cytotoxic quinones and endogenous electrophiles, which may enhance cellular sensitivity to chemotherapeutic agents and oxidative stress. This model is particularly suited for exploring drug resistance mechanisms in gastric cancer, where upregulated detoxification enzymes often confer survival advantages. The knockout can be used to dissect the interplay between carbonyl reductase activity and other adaptive responses, such as DNA damage repair and drug efflux.
Typical applications include expression analysis via Western blotting and RT-qPCR, functional assessment using carbonyl reductase activity assays, and phenotypic characterization through MTT cytotoxicity, ROS detection, and drug sensitivity profiling. These cells facilitate investigations into gastric cancer drug resistance, xenobiotic metabolism, and oxidative stress signaling. For comprehensive technical resources or assistance, contact Ascent Research.
