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

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.

► We examine the impact of Hsp90 inhibitors on the invasion and migration capacity of tumor cells.
► Hsp90 inhibitors act anti-metastatically under normoxia and hypoxia.
► Combined drug-radiation treatment inhibits cell invasion to a much greater extent.
► Hsp90 inhibitors deplete several marker proteins and impair the F-actin modulation.
► A mechanism for the drug-IR mediated inhibition of cell migration is proposed.