The CBR3 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line. This loss-of-function model features targeted disruption of the CBR3 gene using CRISPR/Cas9-mediated gene editing, resulting in a heterogeneous knockout pool. The polyclonal format avoids clonal selection effects and is suited for bulk population analyses of carbonyl reductase 3 function in gastric cancer contexts.
The AGS cell line is an established human gastric adenocarcinoma model originally isolated from a female patient. These cells are widely utilized in gastric cancer research due to their epithelial origin and retention of key signaling pathways relevant to gastric carcinogenesis and therapeutic response. The AGS background provides a clinically relevant platform to examine detoxification mechanisms, drug metabolism, and oxidative stress responses in gastric adenocarcinoma.
CBR3 encodes an NADPH-dependent carbonyl reductase that catalyzes the reduction of a broad spectrum of carbonyl substrates, including reactive aldehydes, ketones, and quinones. This enzyme functions in cellular detoxification networks, and its expression is transcriptionally regulated by the oxidative stress sensor NRF2 and the xenobiotic-activated receptor AhR. CBR3 operates within pathways such as cytochrome P450-mediated metabolism of xenobiotics and glutathione conjugation, interacting with NADPH and other carbonyl reductase family members. Downstream, CBR3-dependent reduction mitigates electrophilic stress, leading to decreased reactive oxygen species (ROS) levels and quinone detoxification, thereby modulating the cellular redox state. Key pathway components include the NRF2/KEAP1 axis and CYP450 enzymes. Disruption of CBR3 eliminates this protective reductase activity, potentially heightening sensitivity to redox-cycling agents and chemotherapeutics.
In the AGS gastric cancer model, CBR3 knockout abrogates the primary NADPH-dependent detoxification of reactive carbonyls and quinones, rendering cells more susceptible to oxidative insult. This loss creates a functional deficiency in the cellular defense against electrophilic compounds, which may translate into enhanced sensitivity to anticancer drugs that induce redox stress. Consequently, the knockout cells serve as a valuable system for probing CBR3’s role in intrinsic and acquired drug resistance in gastric cancer, offering a direct means to assess how carbonyl reductase activity influences tumor cell survival under chemotherapeutic pressure.
Typical research applications include cancer drug resistance studies, xenobiotic metabolism research, oxidative stress response analysis, and chemosensitization screening. Investigators can employ assays such as western blotting for CBR3 protein, RT-qPCR for CBR3 mRNA, cell viability assays with chemotherapeutic drugs, ROS detection assays, and metabolic activity measurements to characterize the knockout phenotype. These cells facilitate the evaluation of CBR3-dependent pathways in gastric cancer and the identification of compounds that exploit the knockout phenotype. For further information, please contact Ascent Research.
