The objective of this study was to evaluate the effects of combination
therapy with
photodynamic therapy (
PDT) and a novel antiangiogenic regimen using
monoclonal antibodies against both
vascular endothelial growth factor receptors (VEGFR)-1 (MF1) and
VEGFR-2 (DC101) on intracranial
glioblastoma xenografts in nude mice. Nude mice bearing intracerebral U87
glioblastoma were treated with
PDT and the antiangiogenic regimen (MF1 and DC101) either alone or in combination, while those left untreated served as
tumor controls.
Tumor volume and animal survival time were analyzed to evaluate the outcome of different treatment modalities. In addition, the immunohistochemical expression of
VEGF in the brain adjacent to the
tumor,
von Willebrand factor (vWF), apoptotic, and proliferative markers in the
tumor area were examined.
PDT or MF1 + DC101 alone significantly reduced the
tumor volume and prolonged the survival time of
glioma-implanted animals. Combined
therapy markedly reduced
tumor volume and increased survival time with significantly better outcomes than both monotherapies. Both vWF and
VEGF levels significantly increased after
PDT while they both significantly decreased after antiangiogenic treatment, compared with no treatment.
PDT plus antiangiogenic treatment led to significant decreases in both vWF and
VEGF expression, compared with
PDT alone. Either
PDT or antiangiogenic treatment alone significantly increased
tumor cell apoptosis compared with no treatment, while combination
therapy resulted in further augmentation of apoptosis. Antiangiogenic treatment with or without
PDT significantly decreased
tumor cell proliferation, compared with either no treatment or
PDT alone. In summary, we demonstrate both significant inhibition of
tumor growth and extended survival of mice treated by the combination
therapy with
PDT and
antiangiogenic agents, compared with each single treatment, suggesting that the combination
therapy may be a promising strategy to improve clinical outcomes in
glioblastoma.