Ear, Nose, & Throat Surgery, Essentia Health, Duluth, MN, U.S.A.
Department of Otolaryngology-Head and Neck Surgery, University of Minnesota, Minneapolis, MN, U.S.A.
Anticancer Res. 2020 Jun;40(6):3071-3080. doi: 10.21873/anticanres.14288.
BACKGROUND/AIM: Head and neck squamous cell carcinoma affects nearly 500,000 people annually. Augmenting PPARγ functional activation is linked with multiple anti-carcinogenic processes in aerodigestive cell lines and animal models. PPARγ/RXRα heterodimers may be key partners in this activation.
CA 9-22 and NA cell lines were treated with the PPARγ agonist ciglitazone and/or the RXRα agonist 9-cis-retinoic acid. PPARγ functional activation, cellular proliferation, apoptosis activity, and phenotype were subsequently analyzed.
Ciglitazone and 9-cis-retinoic acid independently activated PPARγ and down-regulated the carcinogenic phenotype in vitro. Combination treatment significantly augmented these effects, further decreasing proliferation (p<0.0001), and increasing PPARγ functional activation (p<0.0001), apoptosis (p<0.05), and adipocyte differentiation markers (p<0.0001).
The efficacy of the combination of ciglitazone and 9-cis-retinoic acid afforded lowering treatment concentrations while maintaining desired therapeutic outcomes, optimistically supporting the feasibility and practicality of this novel treatment option.
背景/目的：头颈部鳞状细胞癌每年影响近 50 万人。增强过氧化物酶体增殖物激活受体γ（PPARγ）的功能激活与呼吸道和消化道细胞系以及动物模型中的多种抗癌过程有关。PPARγ/RXRα 异二聚体可能是这种激活的关键伙伴。
用 PPARγ 激动剂吡格列酮和/或 RXRα 激动剂 9-顺式视黄酸处理 CA 9-22 和 NA 细胞系。随后分析 PPARγ 功能激活、细胞增殖、凋亡活性和表型。
吡格列酮和 9-顺式视黄酸可独立激活 PPARγ，并在体外下调致癌表型。联合治疗显著增强了这些作用，进一步降低了增殖（p<0.0001），增加了 PPARγ 功能激活（p<0.0001）、凋亡（p<0.05）和脂肪细胞分化标志物（p<0.0001）。
吡格列酮和 9-顺式视黄酸联合使用的疗效降低了治疗浓度，同时保持了所需的治疗效果，乐观地支持了这种新的治疗选择的可行性和实用性。
