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特异性抑制DNMT3A/ISGF3γ相互作用可提高替莫唑胺抑制肿瘤生长的效率。

Specific Inhibition of DNMT3A/ISGF3γ Interaction Increases the Temozolomide Efficiency to Reduce Tumor Growth.

作者信息

Cheray Mathilde, Pacaud Romain, Nadaradjane Arulraj, Oliver Lisa, Vallette François M, Cartron Pierre-François

机构信息

Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.; present address: Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Stockholm 17176, Sweden.

Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer. 8 quai moncousu, BP7021, 44007 Nantes, France.; Université de Nantes, Faculté de Médecine, Département de Recherche en Cancérologie, IFR26, F-4400, Nantes, France.

出版信息

Theranostics. 2016 Aug 25;6(11):1988-1999. doi: 10.7150/thno.9150. eCollection 2016.

DOI:10.7150/thno.9150
PMID:27698935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5039338/
Abstract

DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide). Our data also demonstrates that the disruption of DNMT3A/ISGF3γ interactions increases the efficiency of chemotherapeutic treatment on established tumors in mice. Thus, our data opens a promising and innovative alternative to the development of specific DNMT inhibitors.

摘要

DNA甲基化是基因组的一个基本特征，是药物操纵的一个候选对象，可能具有重要的治疗优势。因此，DNA甲基转移酶（DNMTs）似乎是药物干预的理想靶点。通过关注DNMT3A与DNMT3A结合蛋白（D3A-BP）之间存在的相互作用，我们的研究确定了DNMT3A/ISGF3γ相互作用，例如一种生物标志物，其存在水平与多形性胶质母细胞瘤（放疗加替莫唑胺）传统化疗治疗的不良生存预后和不良反应预后相关。我们的数据还表明，DNMT3A/ISGF3γ相互作用的破坏提高了对小鼠已建立肿瘤的化疗治疗效率。因此，我们的数据为开发特异性DNMT抑制剂开辟了一个有前景的创新选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9196/5039338/ca9c8cf2986f/thnov06p1988g007.jpg
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