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Copyright (c) 2025 Nasrin M Fadhil, Jawad Hasan Kadhim, Hatham W Atwan, Huda A Alwan, Zeenah W Atwan
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Tirzepatide alters oncogenic signaling pathways in colorectal cancer cells in vitro
Corresponding Author(s) : Nasrin M. Fadhil
Cellular and Molecular Biology,
Vol. 71 No. 11: Issue 11
Abstract
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.
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