The HPGD Knockout HCT 116 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population in which the HPGD gene has been disrupted in the human HCT 116 colorectal carcinoma cell line. This model provides a polyclonal loss-of-function system, enabling the study of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) deficiency within a genetically defined cancer background without the need for single-cell clonal isolation. The knockout product format yields a heterogeneous cell population, reflecting the natural variability of CRISPR-mediated gene disruption across the pool, making it suitable for functional genomic screens and bulk population-level analyses of prostaglandin metabolism and tumor biology.
The HCT 116 cell line is an extensively characterized epithelial cell model derived from a human colorectal adenocarcinoma. It harbors well-documented activating mutations in KRAS (G13D) and PIK3CA (H1047R), which drive constitutive oncogenic signaling and make the cells particularly relevant for studying the intersection of growth factor pathways and inflammatory mediators. The cell line??s robust proliferative capacity, ease of genetic manipulation, and established use in colorectal cancer research provide a consistent and reproducible host background for assessing the consequences of HPGD knockout on tumor cell behavior.
HPGD encodes NAD+-dependent 15-PGDH, the enzyme that catalyzes the oxidation of prostaglandin E2 (PGE2) to 15-keto-PGE2, thereby terminating signaling through EP1?CEP4 receptors. Its expression is transcriptionally regulated by PPAR??, IL-1??, TGF-??, and glucocorticoids, and it interacts with the prostaglandin transporter (PGT) and NAD+ for activity. In the knockout cells, loss of 15-PGDH elevates PGE2 levels, which drive downstream EP2/EP4 receptor-mediated activation of ??-catenin and Wnt signaling, as well as cAMP-dependent pathways. Thus, HPGD disruption removes a critical break on prostaglandin metabolism, amplifying arachidonic acid signaling and inflammation-associated transcriptional programs.
In HCT 116 cells, which already possess oncogenic KRAS and PIK3CA mutations, HPGD knockout enhances pro-tumorigenic PGE2 signaling, promoting proliferation, migration, and invasion. The model reflects reduced 15-PGDH observed in colorectal cancers and inflammatory bowel disease, allowing dissection of how impaired prostaglandin inactivation cooperates with mutant oncogenes. The polyclonal population mirrors tumor heterogeneity, making it valuable for studying drug resistance mechanisms.
Researchers can use the HPGD knockout HCT 116 polyclonal cells to study prostaglandin metabolism in colorectal cancer. Key assays include western blotting for 15-PGDH, PGE2 ELISA, LC-MS-based prostaglandin profiling, and RT-qPCR. Functional assessments such as cell proliferation, migration/invasion, cAMP measurement, and ??-catenin reporter assays can delineate oncogenic pathway activation. The model is also suitable for investigating drug resistance and the interplay between inflammatory mediators and oncogenic mutations. For additional details or custom inquiries, contact Ascent Research.
