In lab tests, tirzepatide (a drug used for diabetes and weight loss) changed the activity of several genes in colon cancer cells. It boosted the tumor‑suppressor p53 and the cell‑death gene CASP8, while also raising the inflammation‑related NF‑kB and the growth gene c‑Myc. These mixed signals hint that tirzepatide might influence cancer‑related pathways, but the work was done only in a petri dish.

Obesity prevalence is rapidly increasing worldwide, necessitating diverse treatment approaches ranging from pharmacotherapy to surgical interventions. Tirzepatide, a recently approved dual GIP/GLP-1 receptor agonist, has shown therapeutic promise, but its impact on cancer-related pathways remains unclear. This in vitro study investigated the molecular effects of tirzepatide on colorectal cancer SW48 cells by assessing the expression of key regulatory genes, including NF-kB, p53, c-Myc, and CASP8, after treatment with varying tirzepatide concentrations compared to untreated controls. Results demonstrated significant upregulation of the tumor suppressor gene p53 and the pro-apoptotic gene CASP8 (notably a 68.37-fold increase in one treatment group, P = 0.0002), alongside increased c-Myc expression in higher dose groups. These findings suggest that tirzepatide exerts anti-cancer effects in colorectal cancer cells by suppressing NF-kB-mediated inflammation, activating p53-dependent tumor suppression, and promoting CASP8-mediated apoptosis. The concurrent upregulation of c-Myc with p53 and CASP8 highlights potential context-dependent regulatory mechanisms. Overall, this study provides mechanistic insights into tirzepatide's modulation of oncogenic signaling pathways, supporting its potential role in colon cancer therapeutics.