The FOXO1 Knockout Hep-G2 Cell Line is a CRISPR/Cas9-edited knockout cell line derived from Hep-G2 human hepatocellular carcinoma cells. This loss-of-function model disrupts the FOXO1 gene, eliminating FOXO1 protein expression and enabling dissection of FOXO1-dependent processes.
Hep-G2 is a widely used human liver cancer cell line that retains many hepatocyte functions, including bile acid synthesis, detoxification, and metabolic hormone responses. Derived from a hepatocellular carcinoma, these cells serve as a relevant in vitro model for hepatic physiology, drug metabolism, and liver cancer biology.
FOXO1 is a forkhead box O transcription factor that acts downstream of the insulin/PI3K/AKT signaling cascade. In the absence of growth factor stimulation, FOXO1 localizes to the nucleus and transcriptionally activates gluconeogenic genes such as G6PC and PCK1, as well as cell cycle inhibitor CDKN1B. AKT-mediated phosphorylation promotes FOXO1 binding to 14-3-3 proteins and cytoplasmic sequestration, thereby inhibiting its activity. Additional regulation is provided by SGK, AMPK, SIRT1, and interacting partners including SMAD3, beta-catenin, and CBP/p300. FOXO1 also modulates apoptosis by regulating pro-apoptotic targets BCL2L11 and TNFSF10, placing it at a key node in growth, metabolism, and survival pathways.
In Hep-G2 cells, FOXO1 functions as a critical regulator of hepatic gluconeogenesis and cell cycle progression. Its inactivation via AKT is frequently observed in cancer, and knockout of FOXO1 is expected to reduce expression of gluconeogenic enzymes and cell cycle inhibitors, thereby altering metabolic flux and proliferation control. This model is particularly valuable for dissecting FOXO1??s role in hepatocellular carcinoma and insulin resistance, and for distinguishing AKT-dependent from FOXO1-independent effects.
Researchers can employ this cell line in a variety of assays, including western blotting, RT-qPCR, ChIP-qPCR, apoptosis assays, glucose production assays, proliferation assays, reporter assays, and co-immunoprecipitation. Applications span the investigation of insulin resistance, hepatic gluconeogenesis, liver cancer proliferation, apoptosis mechanisms, and metabolic disease modeling. The FOXO1 Knockout Hep-G2 Cell Line provides a clean genetic background for mechanistic studies and drug target validation. For more information, please contact Ascent Research.
