NVP-AUY922 和 NVP-BEP800 抑制 HSP90 可降低辐照常氧和低氧肿瘤细胞系的迁移和侵袭。

Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines.

机构信息

Department of Radiation Oncology, University of Würzburg, Josef-Schneider-Strasse 11, D-97080 Würzburg, Germany.

出版信息

Cancer Lett. 2013 May 1;331(2):200-10. doi: 10.1016/j.canlet.2012.12.027. Epub 2013 Jan 20.

DOI:10.1016/j.canlet.2012.12.027

Abstract

This study explores the impact of Hsp90 inhibitors NVP-AUY922 and NVP-BEP800 in combination with ionizing radiation (IR) on the migration and invasion of lung carcinoma A549 and glioblastoma SNB19 cells, under normoxia or hypoxia. Independent of oxygen concentration, both drugs decreased the migration and invasion rates of non-irradiated tumor cells. Combined drug-IR treatment under hypoxia inhibited cell invasion to a greater extent than did each treatment alone. Decreased migration of cells correlated with altered expression of several matrix-associated proteins (FAK/p-FAK, Erk2, RhoA) and impaired F-actin modulation. The anti-metastatic efficacy of the Hsp90 inhibitors could be useful in combinational therapies of cancer.

摘要

本研究探讨了热休克蛋白 90（Hsp90）抑制剂 NVP-AUY922 和 NVP-BEP800 联合电离辐射（IR）对常氧或低氧条件下肺腺癌 A549 和神经胶质瘤 SNB19 细胞迁移和侵袭的影响。无论氧浓度如何，这两种药物都降低了未照射肿瘤细胞的迁移和侵袭率。与单独用药相比，低氧条件下联合药物-IR 治疗更能抑制细胞侵袭。细胞迁移减少与基质相关蛋白（FAK/p-FAK、Erk2、RhoA）表达改变和 F-肌动蛋白调节受损相关。Hsp90 抑制剂的抗转移作用可能对癌症的联合治疗有用。