在临床前模型中，丙戊酸改善了小细胞肺癌的二线治疗方案。
Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models.
作者信息
Hubaux Roland, Vandermeers Fabian, Cosse Jean-Philippe, Crisanti Cecilia, Kapoor Veena, Albelda Steven M, Mascaux Céline, Delvenne Philippe, Hubert Pascale, Willems Luc
机构信息
Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA), ULg, Liege, Belgium; Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium.
出版信息
ERJ Open Res. 2015 Oct 19;1(2). doi: 10.1183/23120541.00028-2015. eCollection 2015 Oct.
With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies.
小细胞肺癌（SCLC）的5年生存率低于5%，预后极差，需要改进治疗方法。尽管一线治疗的总体反应良好，但复发频繁，进一步治疗效果不佳。本研究的目的是改善SCLC的二线治疗。在细胞系（细胞凋亡、活性氧以及RNA和蛋白质表达）和小鼠模型（肿瘤发展）中评估了化疗药物的效果。我们在此证明，组蛋白脱乙酰酶抑制剂丙戊酸可提高二线方案（长春地辛、阿霉素和环磷酰胺）对SCLC细胞和小鼠模型的疗效。整合微小RNA和mRNA数据的转录组分析确定了SCLC细胞对丙戊酸反应中的关键信号通路，为改进治疗开辟了新前景。
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