Figure 6.

CAT₃ enhanced antitumor activity of TMZ in TMZ-resistant GBM. (A, B) Cell proliferation inhibition curve of U251/TMZ and T98G cells treated with various concentrations of TMZ alone, or in combination with PF403 (5 nmol/L) or GANT61 (5 µmol/L) for 72 hours. (C) U251/TMZ cells were pretreated with PF403 (5 nM) for 1 h, following the addition of TMZ (250 µmol/L) over 48 hours. Protein levels of Gli1 were detected via immunoblotting. (D) T98G cells were pretreated with PF403 (5 nmol/L) for 1 hour, following the addition of TMZ (250 µmol/L) over 48 hours. Protein levels of Gli1 and MGMT were detected via immunoblotting. (E) MRI T2-weighted image of intracranial tumors from various groups of the U251/TMZ orthotopic model. TMZ was orally administered (50 mg/kg) to mice for 5 days; or CAT₃ (6 mg/kg) was orally administered daily; or a combination (TMZ 50 mg/kg for 5 days + CAT₃ 6 mg/kg daily). (F) Tumor volumes in the U251/TMZ orthotopic mouse model. **P < 0.01, compared to the vehicle group, ANOVA analysis.

Abbreviations: ANOVA, analysis of variance; GBM, glioblastoma multiforme; MGMT, O⁶-methylguanine DNA methyltransferase; TMZ, temozolomide.