Antiangiogenic treatment enhances photodynamic therapy responsiveness in amouse mammary carcinoma

Photodynamic therapy (PDT) is a promising cancer treatment that induces loc alized tumor destruction via the photochemical generation of cytotoxic sing let oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage as well as microvascular injury within exposed tumors. Reduction in vascula r perfusion associated with RUT-mediated microvascular injury produces tumo r tissue hypoxia, Using a transplantable BA mouse mammary carcinoma, we sho w that Photofrin-mediated RUT induced expression of the hypoxia-inducible f actor-1 alpha (HIF-1 alpha) subunit of the heterodimeric HIF-1 transcriptio n factor and also increased protein levels of the HIF-1 target gene, vascul ar endothelial growth factor (VEGF), within treated tumors. HIF-1 alpha and VEGF expression were also observed following tumor clamping, which was use d as a positive control for inducing tissue hypoxia, PDT treatment of BA tu mor cells grown in culture resulted in a small increase in VEGF expression above basal levels, indicating that PDT-mediated hypoxia and oxidative stre ss could both be involved in the overexpression of VEGF, Tumor-bearing mice treated with combined antiangiogenic therapy (IM862 or EMAP-II) and PUT ha d improved tumoricidal responses compared with individual treatments. We al so demonstrated that PDT-induced VEGF expression in tumors decreased when e ither IM862 or EMAP-II was included in the PDT treatment protocol. Our resu lts indicate that combination procedures using antiangiogenic treatments ca n improve the therapeutic effectiveness of PDT.