Bhuvaneswari Ramaswamy, Yuen Gan Yik, Chee Soo Khee, Olivo Malini
National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610.
Photochem Photobiol Sci. 2007 Dec;6(12):1275-83. doi: 10.1039/b705763f. Epub 2007 Nov 5.
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.
光动力疗法（PDT）是一种治疗方式，即局部或全身给予光敏剂，随后用合适波长的光照射以实现选择性组织损伤。此外，PDT是一种耗氧反应，会导致缺氧介导的肿瘤血管破坏，从而实现有效治疗。然而，肿瘤内的缺氧状态会导致与应激相关的血管生成生长因子和细胞因子释放，这种炎症反应可能会通过促进肿瘤再生而降低PDT的疗效。在这种情况下，将血管生成抑制剂纳入治疗方案可提高PDT的有效性。阿瓦斯汀（贝伐单抗）是一种血管内皮生长因子（VEGF）特异性单克隆抗体，与化疗联合使用为转移性结直肠癌患者带来了希望。在本研究中，我们评估了金丝桃素介导的PDT与阿瓦斯汀联合使用对VEGF水平的影响及其对整体肿瘤反应的作用。实验在Balb/c裸鼠皮下建立的膀胱癌异种移植模型上进行。采用抗体芯片、酶联免疫吸附测定（ELISA）和免疫组织化学（IHC）来评估不同治疗组中的VEGF浓度。我们的结果表明，阿瓦斯汀联合PDT进行靶向治疗可提高膀胱肿瘤异种移植模型中的肿瘤反应性。免疫染色显示，在接受PDT与阿瓦斯汀联合治疗的肿瘤中，VEGF表达极少。血管生成蛋白，如血管生成素、碱性成纤维细胞生长因子（bFGF）、表皮生长因子（EGF）和白细胞介素（IL-6和IL-8）在联合治疗组中也被发现下调。
