The ABCB1 Knockout AGS Polyclonal Cells are an AGS human gastric adenocarcinoma cell population with CRISPR/Cas9-mediated disruption of the ABCB1 gene. This polyclonal knockout product provides a heterogeneous pool of cells carrying loss-of-function mutations, avoiding clonal selection artifacts and enabling robust functional studies of multidrug resistance.
The AGS cell line, derived from a gastric adenocarcinoma, is a well-established epithelial model for investigating gastric cancer signaling, drug response, and oncogenic pathways. Its endogenous P-glycoprotein expression makes it a relevant host for dissecting the contributions of ABCB1 to chemoresistance.
The ABCB1 gene encodes the ATP-dependent efflux transporter P-glycoprotein (P-gp), which reduces intracellular accumulation of diverse xenobiotics and anticancer drugs. Transcriptional regulation is controlled by nuclear receptors NR1I2 (PXR) and NR1I3 (CAR) and stress-induced factors including HIF1A and NF-??B. At the plasma membrane, P-gp function requires interactions with ERM proteins (ezrin, radixin, moesin) and caveolin-1. Downstream effects include diminished drug retention, chemoresistance, and altered ceramide glycosylation. P-gp operates alongside ABCG2, MRP1, and drug-metabolizing enzymes such as CYP3A4 and GSTs within broader pharmacoresistance networks.
In AGS gastric cancer cells, ABCB1 knockout abrogates the primary active efflux mechanism for chemotherapeutics like doxorubicin and paclitaxel, sensitizing these cells to drug-induced cytotoxicity. This loss-of-function model facilitates examination of P-gp-dependent resistance, differentiation between intrinsic and acquired resistance mechanisms, and assessment of chemo-sensitization strategies. It preserves gastric adenocarcinoma characteristics, enabling integrated studies of resistance and tumor cell biology.
Key research applications include functional screening of ABCB1 substrates and inhibitors using rhodamine 123 efflux or calcein-AM retention assays, and cytotoxicity evaluation via MTT or similar viability tests. Molecular analyses by western blotting and RT-qPCR quantify transporter expression changes, while flow cytometry measures surface P-gp levels. These cells also support investigation of upstream regulators like NR1I2 and HIF1A in drug resistance signaling. For further technical details, please contact Ascent Research.
