Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in mouse squamous cell carcinoma subjected to photodynamic therapy

Abstract

The kinetics of oxygenation and proliferative activity in mouse squamous cell carcinomas subjected to photodynamic therapy (PDT) were investigated in order to elucidate appropriate fractionation intervals between PDTs for enhanced anti-tumor effects. Tumor reoxygenation following PDT was evaluated in mice by immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). In addition, proliferative activity after PDT was assessed by the immunohistochemical expression of proliferating cell nuclear antigen (PCNA). Both the HIF-1α labeling indices (LIs) and VEGF LIs of tumor cells were increased at 0, 2.5, and 6 hrs after PDT but subsequently decreased at 24 hrs after PDT. The PCNA LI of tumor cells at 24 hrs after PDT was significantly lower than that of the control group but returned to the control level at 48 hrs. These results suggested that tumors subjected to PDT appeared to be hypoxic from immediately to 6 hrs after PDT but subsequently were reoxygenated at 24 hrs after PDT. In conclusion, we propose here that fractionated light exposure with a 24-hrs interval should be utilized in PDT for an enhanced anti-tumor effect.