Significance of HIF-1-active cells in angiogenesis and radioresistance.

摘要: Human solid tumors contain hypoxic regions that have considerably lower oxygen tension than the normal tissues. Hypoxia offers resistance to radiotherapy and anticancer chemotherapy, as well predispose increased tumor metastases. Furthermore, hypoxia induces hypoxia-inducible factor-1 (HIF-1), which in turn increases angiogenesis. Thus, eradication of HIF-1-active/hypoxic cells is very important for cancer therapy. We previously reported procaspase-3 fused with a von Hippel–Lindau (VHL)-mediated protein destruction motif alpha subunit HIF-1 (HIF-1α) containing Pro564, named TAT-ODD-procaspase-3 (TOP3), specifically induced cell death vivo vitro. now report TOP3 also eradicates radiation-induced HIF-1-active cells. activity xenografts human cells, express luciferase under transcriptional control HIF-1, were monitored quantified daily an bioluminescence photon-counting device. was more rapidly by ionizing radiation (IR) compared untreated tumors. efficiently decreased HIF-1-activity irradiated unirradiated ones, indicating eradicated IR hypoxia. Eradication during irradiation exhibited significant suppression angiogenesis strong enhancement long-term growth xenografts. These results further strengthen argument play crucial roles radioresistance.