IL-24 Induces Cell Dormancy and Oxaliplatin Resistance in Colon Cancer Cells by Activating NF-κB Pathway.

Authors

Yanyan Hu, Shengying Li, Minjing Zhu, Chaoju Gong, Zejun Fang

Published in

Molecular carcinogenesis. Jul 16, 2026. Epub Jul 16, 2026.

Abstract

Oxaliplatin-based chemotherapy is a principal treatment for colon cancer, but drug resistance hinders its efficacy. Cancer cell dormancy is reportedly a crucial driver of chemoresistance. IL-24 functions vitally in tumor chemoresistance, yet its role in colon cancer dormancy and oxaliplatin resistance remains unexplored.IL-24 expression was assessed in colon cancer tissues and cells via RT-qPCR, western blotting, or immunohistochemistry. The functions of IL-24 in colon cancer cell proliferation, apoptosis, dormancy, and oxaliplatin resistance were evaluated by CCK-8, flow cytometry, and western blotting. The downstream mechanism of IL-24 was predicted using RNA sequencing and bioinformatics analyses and verified in vitro. A tumor xenograft mouse model was built to further verify the role of IL-24 in colon cancer. IL-24 was overexpressed in oxaliplatin-resistant colon cancer tissues and cells. Furthermore, IL-24 treatment reversed the anti-proliferative and pro-apoptotic effects of oxaliplatin on colon cancer cells. Regarding cell dormancy, IL-24 treatment triggered G0/G1 cell cycle arrest and upregulated dormancy markers (CDKN1A, CDKN1B, TGFB2, and MSK1). Bioinformatics analyses revealed that IL-24 might function in colon cancer mainly through NF-κB pathway, and IL-24 activated the NF-κB axis in tumor cells. Importantly, treatment with NF-κB inhibitor reversed IL-24-induced colon cancer cell dormancy and oxaliplatin resistance. In vivo, IL-24 treatment abolished the anti-tumor effects of oxaliplatin, promoted cell dormancy, and activated NF-κB signaling in tumor tissues. IL-24 induces colon cancer cell dormancy and oxaliplatin resistance by activating NF-κB signaling. The IL-24/NF-κB axis may serve as a likely target to alleviate oxaliplatin resistance in colon cancer.

PMID:
42462113
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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