Differential cytotoxic effect of polybrene on distinct glioblastoma subtypes

Polybrene, also known as a common name hexadimethrine bromide, is a reagent widely used to improve the transduction efficiency of viral vectors. Although polybrene has been used for studying glioblastoma cells, its cytotoxicity on these cells has not been systematically addressed. Glioblastoma is one of the most aggressive types of brain tumors, associated with poor patient prognosis due to its high cellular heterogeneity and resistance to treatment. Glioblastoma is known to consist of multiple subtypes, which represent distinct molecular and cellular characteristics of glioblastoma cells. Due to such differences in their characters, each glioblastoma cell subtype exhibits distinct sensitivity to chemicals. In this study, we show that polybrene reduces cell viability more strongly in neural progenitor cell-like (NPC-like) glioblastoma cells than in mesenchymal-like (MES-like) cells, with increased sensitivity also observed in non-MES-like cell states. This effect in NPC-like cells suggests a possible involvement of calcineurin, a calcium/calmodulin-dependent phosphatase, since inhibition of calcineurin using FK-506 or cyclosporine A (CsA) rescues polybrene-induced cell death. Our findings suggest that polybrene sensitivity scoring could provide a rapid and affordable method for glioblastoma subtype prediction and highlight calcineurin involvement as a potential subtype-associated specific pathway in glioblastoma.