gms | German Medical Science

Objective: Treatment of malignant glioma remains a major clinical challenge. It was the aim of our study to investigate the anti-tumor effects of combined antiangiogenic and temozolomide treatment for malignant glioma.

Methods: SF126 and U87 glioma cells were implanted subcutaneously in nude mice (N = 6 per group) and tumor growth was assessed. Control group received NaCl, TMZ-group received temozolomide (200 mg/kg BW), SU-group received Sunitinib (40 mg/kg BW) and TMZ/SU-group (200mg + 40mg/kg BW) received the combination of both agents. Histological analysis included tumor cell proliferation, endothelial cell proliferation, apoptosis, vessel density and vascular pericyte coverage.

Results: Tumor growth was significantly reduced between treated groups and control group in both cell lines. TMZ/SU resulted in significantly reduced tumor growth compared to either mono treatment (NaCl: 174 ± 38 mm³; TMZ: 106 ± 13 mm³; SU: 114 ± 53 mm³; TMZ/SU: 34 ± 7 mm³). Combination treatment induced significantly increased apoptosis (NaCl: 5 ± 3; TMZ: 58 ± 10; SU: 60 ± 3; TMZ/SU: 80 ± 10) and reduced endothelial cell proliferation (NaCl: 27 ± 7 n/ROI; TMZ: 17 ± 1n/ROI; SU: 13 ± 1 n/ROI; TMZ/SU: 8 ± 2 n/ROI) as compared to either monotherapy. Combined therapy induced a significantly stronger antiangiogenic response as mono antiangiogenic treatment (vessel density SU: 110 ± 15 n/ROI; TMZ/SU: 80 ± 12 n/ROI). Pericyte coverage was significantly increased in tumor vessels in response to combination therapy (NaCl: 90 ± 7%, TMZ: 90 ± 8%, SU: 68 ± 9%, TMZ/SU: 80 ± 9%).

Conclusions: Combined antiangiogenic and temozolomide treatment induces a beneficial anti-glioma response due to additive antiangiogenic and proapoptotic effects. However, combined treatment may aggravate vascular resistance mechanisms.