Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab) improves tumor response by downregulating angiogenic proteins
Hypericin-mediated photodynamic therapy in combination with Avastin (bevacizumab) improves tumor response by downregulating angiogenic proteins
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DOI：
10.1039/b705763f
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发表时间：
2007-01-01
影响因子：
3.1
通讯作者：
Olivo, Malini
中科院分区：
文献类型：
--
作者：
Bhuvaneswari, Ramaswamy;Yuen, Gan Yik;Olivo, Malini
光动力疗法（PDT）是一种治疗方式，其中局部或全身施用光敏剂，然后进行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，其导致缺氧介导的肿瘤血管破坏，从而导致有效的治疗。然而，肿瘤内的缺氧条件可引起血管生成生长因子和细胞因子的应激相关释放，并且这种炎症反应可能通过促进肿瘤再生长而降低PDT的功效。在这种情况下，PDT的有效性可以通过将血管生成抑制剂组合到治疗方案中来增强。血管内皮生长因子（VEGF）特异性单克隆抗体Avastin（贝伐单抗）联合化疗为转移性结直肠癌患者带来了希望。在这项研究中，我们评估了金丝桃素介导的PDT和Avastin对VEGF水平的联合作用及其对整体肿瘤反应的影响。在Balb/c裸鼠皮下建立的膀胱癌异种移植物上进行实验。进行抗体阵列、酶联免疫吸附测定（ELISA）和免疫组织化学（IHC）以评估各个处理组中的VEGF浓度。我们的结果表明，阿瓦斯丁沿着PDT的靶向治疗可以提高膀胱肿瘤异种移植物的肿瘤反应性。免疫组化显示PDT和Avastin联合治疗的肿瘤中VEGF表达最低。血管生成蛋白e.例如，在一个实施例中，还发现在联合治疗组中血管生成素、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）下调。
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.