Fig. 4.

Superoxide dismutase mimetic, Tempol, inhibits cycling hypoxia-induced chemoresistance. a Cytotoxicity assay of normoxia (Nor), uninterrupted hypoxia (NiH), and cycling hypoxia (CyH)-mediated temozolomide (TMZ) sensitivity in U251 and U87 glioblastoma cells. *P < 0.05 compared to Nor with TMZ treatment. b Cytotoxicity assay after Tempol treatment revealed increased TMZ cytotoxicity and suppression of cycling hypoxia (CyH)-mediated TMZ resistance in U251 and U87 glioblastoma cells. *P < 0.05, **P < 0.01, ***P < 0.001 compared to CyH without any treatment, ^###P < 0.001 compared to CyH with TMZ treatment. c Cytotoxicity assay of TMZ in normoxic tumor cells (Hoechst 3342⁺ and GFP⁻), chronic hypoxic tumor cells (Hoechst 3342⁻ and GFP⁺), and cycling hypoxic tumor cells (Hoechst 3342⁺ and GFP⁺) isolated from disaggregated U87/hif-1-r xenografts. *P < 0.05, **P < 0.01 compared to normoxic tumor cells (Hoechst 3342⁺ and GFP⁻). Error bars denote the standard deviation among triplicate experiments