Open Access

ARTICLE

Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

DONGYANG WANG, YI CHEN, JING HUANG, YOU ZHANG, CHONGKUI SUN, YINGQIANG SHEN^*

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Medicine of Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China

* Corresponding Author: YINGQIANG SHEN. Email:

(This article belongs to the Special Issue: Recent Advancement in Cancer Molecular Signaling)

BIOCELL 2023, 47(2), 329-338. https://doi.org/10.32604/biocell.2023.023489

Received 28 April 2022; Accepted 28 July 2022; Issue published 18 November 2022

Abstract

Glucocorticoids (GC) are widely used to counter the adverse events during cancer therapy; nonetheless, previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells, especially in epidermal growth factor receptor (EGFR)-targeted therapy of head and neck squamous cell carcinoma (HNSCC) remaining to be elucidated. The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism. HNSCC cell lines (HSC-3, SCC-25, SCC-9, and H-400) and the human oral keratinocyte (HOK) cell lines were assessed for GC receptor (GR) expression. The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry. Levels of signaling pathways participants GR, mTOR, and EGFR were determined by quantitative polymerase chain reaction and western blotting. GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling. But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway. Besides, GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway. Thus, GCs reduce the efficacy of afatinib on HNSCC, implicating a cautious use of glucocorticoids in clinical practice.

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Keywords

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