Bitter Taste Receptor Agonists Induce Apoptosis in Papillary Thyroid Cancer.

IF 2.3 3区医学 Q1 OTORHINOLARYNGOLOGY Head and Neck-Journal for the Sciences and Specialties of the Head and Neck Pub Date : 2025-03-05 DOI:10.1002/hed.28120

Kimberly Wei, Brianna L Hill, Joel C Thompson, Zoey A Miller, Arielle Mueller, Robert J Lee, Ryan M Carey

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Abstract

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with a 20% recurrence rate. Bitter taste receptors (T2Rs) and their genes (TAS2Rs) may regulate survival in solid tumors. This study examined T2R expression and function in PTC cells.

Methods: Three PTC cell lines (MDA-T32, MDA-T68, and MDA-T85) were analyzed for expression using RT-qPCR and immunofluorescence. Live cell imaging measured calcium responses to six bitter agonists. Viability and apoptosis effects were assessed using crystal violet and caspase 3/7 activation assays. Genome analysis of survival was conducted.

Results: TAS2R14 was consistently highly expressed in all cell lines. Five bitter agonists produced significant cytoplasmic and mitochondrial calcium responses across all cell lines. All bitter agonists significantly decreased viability and induced apoptosis. Higher TAS2R14 expression correlated with better progression-free survival in patients (p < 0.05).

Conclusions: T2R activation by bitter agonists induces apoptosis, and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.

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苦味受体激动剂诱导甲状腺乳头状癌细胞凋亡

背景：甲状腺乳头状癌（PTC甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，复发率为20%。苦味受体（T2Rs）及其基因（TAS2Rs）可能会调节实体瘤的生存。本研究考察了 T2R 在 PTC 细胞中的表达和功能：方法：使用 RT-qPCR 和免疫荧光分析了三种 PTC 细胞系（MDA-T32、MDA-T68 和 MDA-T85）的表达情况。活细胞成像测量了钙对六种苦味激动剂的反应。使用水晶紫和 caspase 3/7 激活试验评估了细胞活力和凋亡效应。对存活率进行了基因组分析：结果：TAS2R14在所有细胞系中都持续高表达。五种苦味激动剂在所有细胞系中都产生了明显的细胞质和线粒体钙反应。所有苦味激动剂都能明显降低细胞活力并诱导细胞凋亡。较高的 TAS2R14 表达量与患者较好的无进展生存期相关（p 结论：TAS2R14 表达量越高，患者的无进展生存期越长：苦味激动剂激活 T2R 可诱导细胞凋亡，TAS2R 的高表达与生存率相关，这表明苦味激动剂在甲状腺癌治疗中具有潜在的治疗意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 医学-耳鼻喉科学

CiteScore

7.00

自引率

6.90%

发文量

278

审稿时长

1.6 months

期刊介绍： Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.