The effect of temozolomide on Hsp60 and Hsp70 expression in extracellular vesicles derived from U87MG glioma cells

Abstract

Objectives: Temozolomide (TMZ) is an effective drug forglioblastoma multiforme (GBM), but the mechanism underlyingTMZresistance is poorly understood. Newevidencehas revealed that the release of heat shock proteins (Hsps)derived from extracellular vesicles (EVs) play an importantrole in cancer progression by modulating tumor microenvironmentand cellular cross-talk. This study aims to evaluatethe effects of TMZ on the expression of EV-derived andcellular Hsps and cell motility in U87MG human glioblastomacell line.Methods: Glial-EVs were isolated from the culture mediumand characterized by SEM and immunoblotting. Theeffect of TMZ treatments (25, 200 and 750 μM) on cell proliferation(MTT assay), migration (scratch assay), andHsp60 and Hsp70 levels (immunoblotting) were evaluated.Results: TMZ treatments led to an increase in intracellularHsp70 while decreasing EV-derived Hsp70. Cellular Hsp60level was elevated at the low dose of TMZ, but it reduced athigher TMZ concentrations. Hsp60 was also decreased inEVs secreted from TMZ-treated cells. Besides, TMZ treatmentreduced the proliferation and migration of gliomacells in a dose-dependent manner.Conclusions: Our results suggest that TMZ has the potentialto target both EV-derived and cellular Hsps for GBMtreatment, thus it may reduce cell motility.