Determination of Vascular Endothelial- and Fibroblast-Growth Factor Receptors in a Mouse Fibrosarcoma Tumor Model Following Photodynamic Therapy

Ziolkowski, Piotr; J.Osiecka, Beata; Symonowicz1, Krzysztof; Chmielewski, Piotr; Latos-Grazynski, Leszek; Bronowicz, Andrzej

Determination of Vascular Endothelial- and Fibroblast-Growth Factor Receptors in a Mouse Fibrosarcoma Tumor Model Following Photodynamic Therapy

Authors

Piotr Ziolkowski

Beata J.Osiecka

Krzysztof Symonowicz1

Piotr Chmielewski

Leszek Latos-Grazynski

Andrzej Bronowicz

Abstract

The role of angiogenic molecules, like vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) in tumor angiogenesis was well confirmed. Photodynamic therapy (PDT) action is, to very high degree, based on tumor vasculature damage. Therefore, it seemed to be important to evaluate growth factor receptors after PDT. The extent of receptor expression was studied by immuno-histochemical method. In this study, vascular endothelial growth factor (VEGFR) receptor and fibroblast growth factor (FGFR-1) receptor have been evaluated at different time points after PDT of tumor-bearing BALB/c mice. Two sensitizers: hematoporphyrin derivative (HpD) and 21, 23-dithiaporphyrin (DTP) were given intraperitoneally in doses: 1.25, 2.5 and 5.0 mg/kg followed by light irradiation at total doses: 50 and 100 J/sq.cm 24 hours later. The number of VEGFR and FGFR-1 in control samples did not exceed 40 per one vessel, whereas after PDT, a significant decrease in number of both receptors was observed. No differences between HpD- and DTP-PDT in anti-receptor activities were observed (p<0.001 for VEGFR and p<0.002 for FGFR-1). The observed decrease in VEGFR and FGFR-1 amount confirms that after PDT, some proteins are inactivated and such a decrease may influence PDT effectiveness

Keywords

Vascular endothelial growth factor receptor (VEGFR)

fibroblast growth factor receptor (FGFR-1)

Angiogenesis

Fibrosarcoma

Photodynamic therapy

Immunohistochemistry