The ALOX12 Knockout HGC-27 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human gastric adenocarcinoma cell line HGC-27, featuring targeted gene disruption of ALOX12. This loss-of-function model abolishes arachidonate 12-lipoxygenase activity, thereby blocking 12-HPETE and 12-HETE production and enabling precise study of eicosanoid-mediated signaling in gastric cancer research.
The HGC-27 host cell line originates from a poorly differentiated human gastric adenocarcinoma and is widely employed as a reliable in vitro model for aggressive gastric cancer. Its molecular profile, which includes aberrant cytokine responses and growth factor signaling, offers a clinically relevant platform for investigating the impact of lipid-metabolizing enzymes on tumor cell behavior, including proliferation, invasion, and drug sensitivity.
ALOX12 catalyzes the dioxygenation of arachidonic acid to 12-HPETE, which is rapidly reduced to 12-HETE, a potent lipid mediator. 12-HETE modulates downstream effectors such as PPAR??, NF-??B, the anti-apoptotic protein Bcl-2, and the ferroptosis suppressor GPX4. Upstream, ALOX12 is regulated by cytokines (IL-1??, TNF-??), the tumor suppressor TP53, and reactive oxygen species. The enzyme physically interacts with PEBP1 to facilitate lipid peroxidation, and its activity is counterbalanced by GPX4. Within the broader arachidonic acid cascade, ALOX12 functions alongside ALOX5, PTGS2 (COX-2), and cytochrome P450 enzymes to determine cellular lipid mediator profiles and ferroptosis susceptibility.
In gastric carcinoma, ALOX12-derived 12-HETE has been implicated in driving tumor progression, metastasis, and resistance to chemotherapy by activating NF-??B-mediated survival signals and Bcl-2-regulated anti-apoptotic pathways. The HGC-27 ALOX12 knockout cells provide a dedicated model to dissect these oncogenic mechanisms in the context of a poorly differentiated gastric adenocarcinoma background. Furthermore, the knockout allows exploration of how ALOX12 loss influences ferroptosis sensitivity through the PEBP1?CGPX4 axis, offering insights into lipid peroxidation-driven cell death as a therapeutic vulnerability.
Typical applications include ferroptosis induction with erastin or RSL3, real-time lipid peroxidation monitoring via C11-BODIPY staining, cell viability and apoptosis analysis by flow cytometry, and migration/invasion assays. Knockout validation is achievable through western blotting and RT-qPCR, and researchers can assess compensatory changes in ALOX5 or PTGS2 expression. This polyclonal knockout population is also suited for drug resistance screens and lipid signaling pathway studies in gastric cancer. For further information, please contact Ascent Research.
