Fig. 3

Ibrutinib hinders glioma cell migration and Abcb1 efflux and viability in combination with doxil. Varied ibrutinib dosing does not influence S635 rat glioma cell viability after 24 h (a). Glioma cell migration was influenced greatest by 10 µM ibrutinib 36–48 h after treatment compared with control and 1 µM therapy as evidenced by decreased cell migration to serum containing fetal bovine-serum (*p < 0.05) (b). Rhodamine efflux as a measure of Abcb1 function demonstrates both 10 µM ibrutinib effectively decreased efflux akin to known inhibitor valspodar (c). Combination therapy of ibrutinib with doxil found dose-dependent cooperation to hinder cell viability after 48 h exposure to therapy (***p < 0.001****p < 0.0001) (d). Combined ibrutinib (10 µM) and doxil (10 and 100 µM) resulted in increased caspase3/7 apoptosis activity compared with single therapy (****p < 0.0001) (e)