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

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2025-01-22 DOI:10.1002/btm2.10741
Christian R. Moya‐Garcia, Meghana Munipalle, Alain Pacis, Nader Sadeghi, Maryam Tabrizian, Nicole Y. K. Li‐Jessen
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Abstract

Tumor 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.
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建立化疗耐药喉癌细胞模型,通过转录组学分析和肿瘤芯片平台研究化疗耐药和化疗致敏反应
肿瘤耐药是头颈部鳞状细胞癌复发的常见原因。本研究的目的是建立和表征一种化疗耐药喉癌细胞模型,并测试其在化疗增敏治疗中的潜在效用。在基因型水平上,RNA测序证实细胞获得了假定的耐多西他赛(DR)基因(如TUBB3、CYP24A1)和信号通路(如PI3K/mTOR、自噬)上调的耐药。为了进行表型分析,DR细胞与喉成纤维细胞在模拟体内缺氧肿瘤核心的2通道微流控芯片中共培养。用化学增敏剂二甲双胍(MTF)对喉部肿瘤芯片进行药物敏感性试验。与未处理的对照组相比,MTF引发的癌细胞对多西紫杉醇(DTX)表现出更高的敏感性,即细胞死亡。总的来说,这种耐药获得性细胞模型显示了化疗耐药的基因型和表型特征,为测试恢复肿瘤对DTX敏感性的新治疗策略提供了可行的选择。
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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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