The CBR1 Knockout A2780 Polyclonal Cells represent a CRISPR/Cas9-mediated gene-disrupted polyclonal cell population generated from the A2780 human ovarian cancer cell line, featuring targeted inactivation of the carbonyl reductase 1 (CBR1) gene.
The parental A2780 line was established from an untreated patient with ovarian endometrioid carcinoma and displays epithelial morphology with sensitivity to platinum-based agents. A2780 cells serve as a well-characterized model for studying mechanisms of chemotherapeutic resistance, particularly to platinum drugs and anthracyclines, and are widely employed in xenograft tumorigenesis assays to evaluate therapeutic interventions in vivo.
CBR1 encodes an NADPH-dependent carbonyl reductase that reduces a broad spectrum of endogenous and xenobiotic carbonyl substrates, including the anthracycline doxorubicin (to its metabolite doxorubicinol) and prostaglandin E2 (to PGF2??). This enzymatic activity is positioned downstream of oxidative stress responses regulated by NFE2L2 (NRF2) and is modulated by glucocorticoid receptor signaling and the lipid-sensing nuclear receptor PPAR-alpha. Within the arachidonic acid cascade, CBR1 cooperates with PTGS2 (COX-2) and HPGD to determine prostaglandin profiles, while interactions with multidrug resistance mediators such as ABCC1 and the aldo-keto reductase AKR1C3 influence cellular detoxification and drug distribution. CBR1 utilizes NADPH as a cofactor and may undergo homodimerization, with substrate specificity governed by its binding pocket architecture.
In the A2780 ovarian cancer model, CBR1 expression contributes to the metabolic inactivation of anthracyclines and the scavenging of cytotoxic lipid peroxidation products such as 4-hydroxynonenal, thereby promoting cell survival under chemotherapeutic and oxidative stress. Disruption of CBR1 in these polyclonal knockout cells provides a controlled system to dissect the enzyme??s impact on doxorubicin sensitivity, prostaglandin signaling, and the cellular antioxidant response. This model is particularly relevant for investigating the intersection of drug metabolism and redox balance in epithelial ovarian tumors, where alterations in carbonyl-reducing pathways have been linked to treatment failure and disease progression.
Researchers can utilize these polyclonal knockout cells for RT-qPCR and Western blotting to confirm CBR1 disruption, enzymatic activity assays with substrates like menadione, and HPLC-based doxorubicin reduction assays. Cell viability and apoptosis analyses following doxorubicin exposure directly evaluate chemoresistance, while prostaglandin E2 metabolite profiling clarifies inflammatory signaling modulation. Immunofluorescence, siRNA comparative studies, and functional rescue experiments further extend utility, and the cells are suitable for inhibitor screening and pharmacogenomic investigations. For further information or technical support, please contact Ascent Research.
