Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, and Department of Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
Oncol Rep. 2011 Sep;26(3):681-6. doi: 10.3892/or.2011.1318. Epub 2011 May 25.
Previous studies have shown that pigment epithelium-derived factor (PEDF) is an antitumor candidate with anti-oxidative, anti-inflammatory and anti-angiogenesis properties. However, the effect of PEDF on gastric carcinoma has not been elucidated. MTT assay and Annexin V/PI staining were performed. Immunohistochemistry was applied to detect microvessel density (MVD) of a xenograft model. The protein levels of vascular endothelial growth factor (VEGF) were examined by western blot analysis and hypoxia-inducible factor-1α (HIF-1α) translocation was investigated by immunofluorescence. Results showed that growth and angiogenesis of gastric carcinoma were suppressed after PEDF injection. PEDF could not directly suppress proliferation or induce apoptosis of gastric carcinoma cells. However, the expression of VEGF both in tumor tissues and gastric carcinoma cells was down-regulated by PEDF. The amount and nuclear translocation of HIF-1α, the transcription factor of VEGF, was also inhibited by PEDF. In conclusion, PEDF suppresses angiogenesis and growth of gastric carcinoma by down-regulating HIF-1α and VEGF and may have potential for gastric carcinoma treatment.
先前的研究表明,色素上皮衍生因子(PEDF)是一种具有抗氧化、抗炎和抗血管生成特性的抗肿瘤候选物。然而,PEDF 对胃癌的影响尚未阐明。进行了 MTT 检测和 Annexin V/PI 染色。免疫组织化学用于检测异种移植模型的微血管密度(MVD)。通过 Western blot 分析检测血管内皮生长因子(VEGF)的蛋白水平,并通过免疫荧光法研究缺氧诱导因子-1α(HIF-1α)易位。结果表明,PEDF 注射后抑制了胃癌的生长和血管生成。PEDF 不能直接抑制胃癌细胞的增殖或诱导其凋亡。然而,PEDF 下调了肿瘤组织和胃癌细胞中 VEGF 的表达。作为 VEGF 的转录因子,HIF-1α 的量和核易位也被 PEDF 抑制。总之,PEDF 通过下调 HIF-1α 和 VEGF 抑制胃癌的血管生成和生长,可能具有治疗胃癌的潜力。