Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab) improves tumor response by downregulating angiogenic proteins.
Photodynamic therapy (PDT) is a therapeutic modality in which a photosensitizer is locally or systemically administered followed by light irradiation of suitable wavelength to achieve selective tissue damage. In addition, PDT is an oxygen-consuming reaction, that causes hypoxia mediated destruction of tumor vasculature that results in effective treatment. However, the hypoxic condition within tumors can cause stress-related release of angiogenic growth factors and cytokines and this inflammatory response could possibly diminish the efficacy of PDT by promoting tumor regrowth. In such circumstances, PDT effectiveness can be enhanced by combining angiogenesis inhibitors into the treatment regimen. Avastin (bevacizumab), a vascular endothelial growth factor (VEGF) specific monoclonal antibody in combination with chemotherapy is offering hope to patients with metastatic colorectal cancer. In this study we evaluated the combination of hypericin-mediated PDT and Avastin on VEGF levels as well as its effect on overall tumor response. Experiments were conducted on bladder carcinoma xenografts established subcutaneously in Balb/c nude mice. Antibody array, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups. Our results demonstrated that the targeted therapy by Avastin along with PDT can improve tumor responsiveness in bladder tumor xenografts. Immunostaining showed minimal expression of VEGF in tumors treated with combination therapy of PDT and Avastin. Angiogenic proteins e.g., angiogenin, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and interleukins (IL-6 and IL-8) were also found to be downregulated in groups treated with combination therapy.
Bhuvaneswari
Ramaswamy
R
National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610. dmsmcd@nccs.com.sg
Yuen
Gan Yik
GY
Chee
Soo Khee
SK
Olivo
Malini
M
D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy*; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D042501:Angiogenic Proteins; D000873:Anthracenes; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017319:Photosensitizing Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D010569:Perylene; C004965:hypericin