Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor‐on‐a‐chip platform

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AbstractTumor resistance to chemotherapy is a common cause of cancer recurrence in patients with head and neck squamous cell carcinoma. The goal of this study is to establish and characterize a chemoresistant laryngeal cancer cell model and test its potential utility for chemosensitizing therapy. At the genotypic level, RNA sequencing confirmed that the cells acquired putative resistance with upregulated docetaxel‐resistant (DR) genes (e.g., TUBB3, CYP24A1) and signaling pathways (e.g., PI3K/mTOR, autophagy). For phenotypic analysis, DR cells were co‐cultured with laryngeal fibroblasts in a 2‐channel microfluidic chip that mimics a hypoxic tumor core in vivo. A drug sensitivity test with a chemosensitizer, metformin (MTF), was performed on the laryngeal tumor‐on‐a‐chip. Compared to non‐treated controls, MTF‐primed cancer cells exhibit higher sensitivity to docetaxel (DTX), that is, cell death. Collectively, this resistance‐acquired cell model displayed presumed genotypic and phenotypic profiles of chemoresistance providing a viable option for testing new therapeutic strategies for restoring tumor sensitivity to DTX.