Tirzepatide Suppresses NF-κB Gene Expression in Colorectal Cancer Cells In Vitro

Overweight and obesity prevalence is in surge globally between 1990 and 2021. One billion male and 1.11 billion female are either overweight or obese This study investigates the in vitro effect of the dual GIP and GLP-1 receptor agonist Tirzepatide on the gene expression of nuclear factor kappa B (NF-κB), a transcription factor critically involved in inflammation and carcinogenesis. Given the potential link between incretin-based therapies and cancer risk, we hypothesizes that Tirzepatide might upregulate NF-κB. Colorectal SW48 cells are treated with three concentrations of Tirzepatide (0.05, 0.5, and 5 µg/µl) for 24 hours. RNA are extracted, cDNA is synthesized, and gene expression is quantified using qPCR. Contrary to the initial hypothesis, results demonstrated a significant, dose-dependent downregulation of NF-κB gene expression. The most substantial suppression (0.03-fold change) are observed at the 0.5 µg/µl concentration, suggesting a non-linear, optimal dose-response relationship. These findings indicate that Tirzepatide exerts a direct anti-inflammatory effect by inhibiting NF-κB signaling in a controlled cellular environment. The observed suppression contrasts with clinical concerns, suggesting that any associated cancer risk may arise from secondary, systemic pathological factors rather than a direct oncogenic effect of the drug. This study highlights Tirzepatide's potential cytoprotective role through NF-κB pathway inhibition.