首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226.
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3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226.

机译:粘着斑激酶抑制剂TAE226对人类头颈部鳞状细胞癌细胞的3D细胞培养物进行放射增敏。

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BACKGROUND AND PURPOSE: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. MATERIALS AND METHODS: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1mum; 1 or 24h) without or in combination with irradiation (0-6Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. RESULTS: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. CONCLUSIONS: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.
机译:背景与目的:黏着斑激酶(FAK)是整联蛋白信号传导和存活的主要参与者,在人类癌症中经常过度表达,因此被假定为癌症治疗的潜在靶标。这项研究的目的是评估FAK抑制剂TAE226在三维(3D)肿瘤细胞培养物中的放射增敏潜力。材料与方法:头颈部鳞状细胞癌(HNSCC)细胞(FaDu,UT-SCC15,UT-SCC45),肺癌细胞(A549),结直肠癌细胞(DLD-1,HCT-116)和胰腺肿瘤细胞(用不同浓度的TAE226(0-1微米; 1或24h)处理MiaPaCa2,Panc1,不使用或联合使用照射(0-6Gy,X射线,单剂量)。随后,进行了3​​D克隆形成存活测定(富含层粘连蛋白的细胞外基质)和蛋白质印迹(表达/磷酸化,例如FAK,Akt,ERK1 / 2)。结果:所有研究的3D细胞培养均显示出TAE226对克隆形成存活的剂量依赖性降低。有趣的是,TAE226仅对3D HNSCC细胞进行了显着放射增敏,并伴有FAK,Akt和ERK1 / 2的明显去磷酸化。结论:我们的数据证明TAE226是有效的FAK抑制剂,可增强3D细胞培养模型中生长的HNSCC细胞的细胞放射敏感性,尤其是。未来的体外和体内研究将阐明,这种方法在多大程度上可能与HNSCC的放射治疗在临床上相关。

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