Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma.
Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma.
复制标题
DOI：
--
复制
发表时间：
2000-08
期刊：
影响因子：
11.2
通讯作者：
A. Ferrario;K. V. Tiehl;N. Rucker;M. Schwarz;P. Gill;C. Gomer
中科院分区：
文献类型：
--
作者：
A. Ferrario;K. V. Tiehl;N. Rucker;M. Schwarz;P. Gill;C. Gomer
光动力疗法（PDT）是一种有前途的癌症治疗，其通过光化学产生细胞毒性单线态氧来诱导局部肿瘤破坏。PDT介导的氧化应激直接导致肿瘤细胞损伤以及暴露肿瘤内的微血管损伤。与PDT介导的微血管损伤相关的血管灌注减少产生肿瘤组织缺氧。使用可移植的BA小鼠乳腺癌，我们表明，Photofrin介导的PDT诱导表达的低氧诱导因子-1 α（HIF-1 α）亚基的异二聚体HIF-1转录因子，并增加蛋白水平的HIF-1靶基因，血管内皮生长因子（VEGF），在治疗的肿瘤。在肿瘤钳夹后也观察到HIF-1 α和VEGF表达，其用作诱导组织缺氧的阳性对照。PDT治疗培养中生长的BA肿瘤细胞导致VEGF表达高于基础水平的小幅增加，表明PDT介导的缺氧和氧化应激都可能参与VEGF的过表达。与单独治疗相比，联合抗血管生成治疗（IM 862或EMAP-II）和PDT治疗的荷瘤小鼠具有改善的杀肿瘤反应。我们还证明，当在PDT治疗方案中包括IM 862或EMAP-II时，PDT诱导的肿瘤中VEGF表达降低。我们的研究结果表明，使用抗血管生成治疗的组合程序可以提高PDT的治疗效果。
Photodynamic therapy (PDT) is a promising cancer treatment that induces localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage as well as microvascular injury within exposed tumors. Reduction in vascular perfusion associated with PDT-mediated microvascular injury produces tumor tissue hypoxia. Using a transplantable BA mouse mammary carcinoma, we show that Photofrin-mediated PDT induced expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) subunit of the heterodimeric HIF-1 transcription factor and also increased protein levels of the HIF-1 target gene, vascular endothelial growth factor (VEGF), within treated tumors. HIF-1alpha and VEGF expression were also observed following tumor clamping, which was used as a positive control for inducing tissue hypoxia. PDT treatment of BA tumor cells grown in culture resulted in a small increase in VEGF expression above basal levels, indicating that PDT-mediated hypoxia and oxidative stress could both be involved in the overexpression of VEGF. Tumor-bearing mice treated with combined antiangiogenic therapy (IM862 or EMAP-II) and PDT had improved tumoricidal responses compared with individual treatments. We also demonstrated that PDT-induced VEGF expression in tumors decreased when either IM862 or EMAP-II was included in the PDT treatment protocol. Our results indicate that combination procedures using antiangiogenic treatments can improve the therapeutic effectiveness of PDT.