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

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2023-06, Vol.166, p.156155-156155, Article 156155
• Main Authors: Joshi, Swarali, Pandey, Ritu, Kumar, Ashok, Gupta, Vikas, Arya, Neha
• Format: Article
• Language: English
• Subjects: Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemoresistance; Cisplatin - pharmacology; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Interleukin-8; Interleukin-8 - pharmacology; Metastasis; Mouth Neoplasms - metabolism; NF-kappa B; NFκB; OSCC; Proto-Oncogene Proteins c-akt - metabolism; Tumor Microenvironment
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2023.156155

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. 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. IL-8 plays a crucial role in OSCC metastasis and its targeted blockade can help in management of cisplatin resistance.