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首页> 外文期刊>Cancer science. >Combination of pigment epithelium‐derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis
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Combination of pigment epithelium‐derived factor with radiotherapy enhances the antitumor effects on nasopharyngeal carcinoma by downregulating vascular endothelial growth factor expression and angiogenesis

机译：色素上皮来源的因子与放射疗法的结合通过下调血管内皮生长因子的表达和血管生成来增强对鼻咽癌的抗肿瘤作用

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AbstractNasopharyngeal carcinoma (NPC), which has the highest incidence in South China, is mainly treated by radiotherapy. However, the survival rate remains low. Angiogenesis is closely correlated with progress of NPC. Thus, the combination of anti-angiogenesis with radiation is an attractive strategy for NPC treatment. A heterogenic xenografted human NPC nude mice model was established to investigate the effect of pigment epithelium-derived factor (PEDF), a potent anti-angiogenic factor, and the combined effect of PEDF and radiotherapy on nasopharyngeal carcinoma. Pigment epithelium-derived factor remarkably suppressed the growth of NPC by 43.52% and decreased the tumor microvessel density (MVD). Pigment epithelium-derived factor had no effects on the proliferation and apoptosis of NPC cell lines by MTT and flow cytometry assay. However, PEDF decreased vascular endothelial growth factor (VEGF) in NPC cell lines by downregulation of hypoxia-inducible factor 1α, a crucial transcriptional factor for VEGF expression, as demonstrated by western blotting and immunofluorescent staining assay. Interestingly, irradiation alone could also effectively downregulate VEGF and MVD of xenografted tumor, which indicates that irradiation suppresses NPC not only by killing tumor cells but also through anti-angiogenesis. Furthermore, combined treatment of PEDF with irradiation enhanced the antitumor efficacy. The MVD and VEGF in the combined therapy were much less than in the treatment with PEDF or radiotherapy alone. Our observation demonstrated that the combination of PEDF with radiotherapy enhances the efficacy of the antitumor effect on NPC by the coordinated inhibition on angiogenesis, which implies the potential role of PEDF as an adjuvant agent for NPC treatment. (Cancer Sci 2011; 102: 1789–1798)
机译：摘要鼻咽癌（NPC）在华南地区发病率最高，主要采用放射疗法治疗。但是，存活率仍然很低。血管生成与NPC的进展密切相关。因此，抗血管生成与放射的结合是用于NPC治疗的有吸引力的策略。建立异种异种移植的人NPC裸鼠模型，以研究色素上皮衍生因子（PEDF），有效的抗血管生成因子的作用以及PEDF与放射疗法联合治疗鼻咽癌的作用。色素上皮衍生因子显着抑制了NPC的生长43.52％，并降低了肿瘤微血管密度（MVD）。通过MTT和流式细胞术测定，色素上皮衍生因子对NPC细胞系的增殖和凋亡没有影响。但是，PEDF通过下调缺氧诱导因子1α（一种表达VEGF的关键转录因子）而降低了NPC细胞系中的血管内皮生长因子（VEGF），这已通过Western印迹和免疫荧光染色实验证实。有趣的是，单独照射也可以有效地下调异种移植肿瘤的VEGF和MVD，这表明照射不仅通过杀死肿瘤细胞而且通过抗血管生成抑制NPC。此外，PEDF与放射线的联合治疗可增强抗肿瘤功效。联合疗法中的MVD和VEGF远低于单独使用PEDF或放射疗法的情况。我们的观察表明，PEDF与放疗的结合通过对血管生成的协同抑制作用增强了对NPC的抗肿瘤作用，这暗示了PEDF作为NPC治疗的辅助剂的潜在作用。 （Cancer Sci 2011; 102：1789-1798）

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