类视黄醇增强口腔癌细胞中噻唑烷二酮 PPARγ 的激活作用。

Retinoids Augment Thiazolidinedione PPARγ Activation in Oral Cancer Cells.

机构信息

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.

出版信息

Anticancer Res. 2020 Jun;40(6):3071-3080. doi: 10.21873/anticanres.14288.

DOI:10.21873/anticanres.14288

PMID:32487601

Abstract

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.

MATERIALS AND METHODS

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.

RESULTS

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).

CONCLUSION

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.

摘要

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。