The CBR3 knockout HT29 polyclonal cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the HT29 human colorectal adenocarcinoma cell line. These cells harbor a targeted disruption of the CBR3 locus, resulting in loss of functional carbonyl reductase 3 protein. The polyclonal nature preserves genetic variability within the population while ensuring consistent knockout phenotypes across experiments. This product serves as a versatile tool for studying the biological roles of CBR3 in colorectal cancer, particularly in the context of xenobiotic metabolism and oxidative stress responses.
HT29 is a widely utilized human colorectal adenocarcinoma cell line exhibiting epithelial morphology. Originally isolated from a primary tumor, HT29 cells have become a cornerstone model in colorectal cancer research, valued for their reproducible growth characteristics and ability to recapitulate key aspects of colon cancer biology. These cells are extensively employed in drug metabolism studies, providing a physiologically relevant system to investigate chemotherapeutic agent processing and resistance mechanisms.
CBR3 encodes a NADPH-dependent carbonyl reductase that catalyzes the reduction of carbonyl groups on diverse xenobiotic and endogenous substrates, including prostaglandins and anthracycline chemotherapeutics. Its expression is transcriptionally regulated by NRF2, AhR, and HIF1A in response to oxidative stress, positioning CBR3 at the intersection of detoxification pathways and redox homeostasis. The enzyme interacts directly with cofactor NADPH and substrates such as doxorubicin, daunorubicin, and prostaglandin E2. In the broader signaling network, CBR3 functions alongside CBR1, AKR1C3, and NQO1, intersecting with CYP450-mediated metabolism and the PTGS2/PTGES prostaglandin synthesis axis.
In the HT29 colorectal cancer context, CBR3 knockout provides a powerful model to dissect mechanisms of chemoresistance. Ablation of CBR3 disrupts the NADPH-dependent inactivation of anthracycline drugs, potentially enhancing cytotoxicity. Concurrently, altered prostaglandin metabolism may modulate tumor-associated inflammation and microenvironment signaling. This model enables detailed investigation of the NRF2-mediated oxidative stress response and its contributions to drug detoxification, offering insights into how colorectal cancer cells adapt to therapeutic pressure.
This knockout model supports a broad spectrum of applications, including drug resistance studies, chemosensitivity testing, and redox biology exploration. Researchers may conduct cell viability assays (MTT) to evaluate responses to doxorubicin, validate CBR3 disruption by Western blot or RT-qPCR, perform apoptosis assays via flow cytometry, or measure ROS levels to assess oxidative stress. These cells are well-suited for high-throughput screening of compounds that modulate carbonyl reductase activity or for unraveling CBR3-dependent signaling in colorectal cancer progression. For further information, please contact Ascent Research.
