Bhuvaneswari Ramaswamy, Gan Yap Yik-Yuen, Yee Karen Kar Lye, Soo Khee Chee, Olivo Malini
National Cancer Centre Singapore, Singapore 169610.
Int J Mol Med. 2007 Oct;20(4):421-8.
Photodynamic therapy (PDT) is currently being used as an alternative treatment modality for various types of cancers. PDT involves the selective uptake and retention of a photosensitizer in the tumor followed by light irradiation of an appropriate wavelength to cause the destruction of tumor cells by the formation of cytotoxic reactive oxygen species. The photosensitizer, hypericin, has shown great potential due to its light-dependent tumor destructive properties. However, as hypericin-mediated PDT primarily targets tumor vasculature, it induces certain pro-angiogenic factors such as vascular endothelial growth factor (VEGF) in the tumor tissue as a result of hypoxia. This study examines the role of hypericin-mediated photodynamic therapy in stimulating the expression of key angiogenesis growth factor VEGF in order to elucidate the process of tumor angiogenesis in nasopharyngeal carcinoma xenografts. We also investigated the effect of angiogenesis inhibitor celebrex on human VEGF levels when combined with hypericin-PDT. These studies were conducted on an in vivo human nasopharyngeal xenograft model. VEGF was measured in the control and hypericin-PDT treated tumors. VEGF levels were found to be higher when the tumors were treated at a 1-h drug-light interval compared to a 6-h interval, due to extensive vascular damage. At 72 h post hypericin-PDT, VEGF levels were upregulated indicating the initiation of regrowth in tumors. The use of angiogenesis inhibitor, celebrex, along with hypericin-PDT downregulated the human VEGF levels suggesting that angiogenesis inhibitors can be used to improve the outcome of hypericin-PDT in nasopharyngeal carcinomas.
光动力疗法(PDT)目前正被用作多种癌症的替代治疗方式。PDT包括肿瘤中光敏剂的选择性摄取和滞留,随后用适当波长的光照射,通过形成细胞毒性活性氧来破坏肿瘤细胞。光敏剂金丝桃素因其光依赖性肿瘤破坏特性而显示出巨大潜力。然而,由于金丝桃素介导的PDT主要靶向肿瘤血管系统,缺氧会导致肿瘤组织中诱导某些促血管生成因子,如血管内皮生长因子(VEGF)。本研究探讨金丝桃素介导的光动力疗法在刺激关键血管生成生长因子VEGF表达中的作用,以阐明鼻咽癌异种移植瘤中的肿瘤血管生成过程。我们还研究了血管生成抑制剂塞来昔布与金丝桃素-PDT联合使用时对人VEGF水平的影响。这些研究是在体内人鼻咽癌异种移植模型上进行的。在对照和金丝桃素-PDT处理的肿瘤中测量VEGF。由于广泛的血管损伤,与6小时间隔相比,在1小时药物-光照间隔处理肿瘤时,VEGF水平更高。在金丝桃素-PDT后72小时,VEGF水平上调,表明肿瘤开始再生。血管生成抑制剂塞来昔布与金丝桃素-PDT联合使用可下调人VEGF水平,这表明血管生成抑制剂可用于改善金丝桃素-PDT在鼻咽癌中的治疗效果。