Targeted blockade of interleukin-8 negates metastasis and chemoresistance via Akt/Erk-NFκB axis in oral cancer.

Autor: Joshi S; Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India., Pandey R; Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India., Kumar A; Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India., Gupta V; Department of Otorhinolaryngology (ENT) - Head & Neck Surgery, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India., Arya N; Department of Medical Devices, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India; Department of Translational Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India. Electronic address: neha.arya@gmail.com.
Jazyk: angličtina
Zdroj: Cytokine [Cytokine] 2023 Jun; Vol. 166, pp. 156155. Date of Electronic Publication: 2023 Apr 21.
DOI: 10.1016/j.cyto.2023.156155
Abstrakt: Background: The tumor microenvironment plays a significant role in tumor growth, metastasis and chemoresistance via dysregulated signaling pathways. Toward this, an inflammatory chemokine, interleukin-8 (IL-8), is overexpressed in various cancers and is involved in tumor progression and chemoresistance. However, the mechanistic role of IL-8 in mediating metastasis and chemoresistance in oral squamous cell carcinoma (OSCC) is not known.
Methods and Results: In the present study, we evaluated the effect of IL-8 in regulating metastasis as well as chemoresistance in OSCC cell lines. For this, IL-8 was blocked exogenously using neutralizing IL-8 monoclonal antibody and IL-8 levels were enhanced by exogenous supply of recombinant human IL-8 (rhIL-8) to OSCC cells. The epithelial-to-mesenchymal transition (EMT) was evaluated using qPCR, migration by scratch/wound healing assay and invasion ability using transwell assay. rIL-8 induced chemoresistance was studied by apoptosis assay and the nuclear localization of NFκB using immunocytochemistry. IL-8 was significantly overexpressed in OSCC patients and cell lines. While exogenous blockade of IL-8 significantly reduced EMT, migration and invasion potential in OSCC cells, IL-8 overexpression upregulated these cellular traits thereby confirming the role of IL-8 in OSCC metastasis. Exogenous blockade of IL-8 also reversed chemoresistance in cisplatin resistant OSCC subline via NFκB signaling.
Conclusion: IL-8 plays a crucial role in OSCC metastasis and its targeted blockade can help in management of cisplatin resistance.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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