Inhibition of Vascular Endothelial Growth Factor Receptor Signaling Leads to Reversal of Tumor Resistance to Radiotherapy

摘要: Certain refractory neoplasms, such as glioblastoma multiforme (GBM) and melanoma, demonstrate a resistant tumor phenotype in vivo. We observed that these models (GBM melanoma) contain blood vessels are relatively to radiotherapy. To determine whether the vascular endothelial growth factor receptor-2 (Flk-1/KDR) may be therapeutic target improve effects of radiotherapy, we used soluble extracellular component Flk-1 (ExFlk), which blocks binding receptor expressed on endothelium. Both sFlk-1 Flk-1-specifc inhibitor SU5416 eliminated resistance GBM melanoma microvasculature determined by both window Doppler flow methods. Human microendothelial cells human umbilical vein showed minimal radiation-induced apoptosis. The antagonists reverted cell apoptosis-prone phenotype. also radiation-sensitive after treatment with 3 Gy. These findings microenvironment including survival tumor-associated contributes vessel therapy.