过氧化物酶增殖体受体γ调节血管内皮生长因子D的表达

Peroxisome proliferator-activated receptor-V modulating vascular endothelial growth factor-D ex-pression

目的探讨活化后的过氧化物酶增殖体受体1（PPAR一1）对血管内皮生长因子D（VEGF．D）的调节作用及其机制。方法用200、100、50、0umol／L浓度的罗格列酮（ROS）干预胃癌BGC一823细胞48h后，分别用细胞免疫组织化学法、Westernblot法检测细胞株中第10号染色体上缺失与张力蛋白同源的磷酸酯酶基因抑癌基因（PTEN）、VEGF—D的表达。用干预后的细胞注射裸鼠建立胃癌移植瘤模型，免疫组织化学法检测瘤体组织中PTEN、VEGF．D的表达。结果细胞免疫组织化学、裸鼠瘤组织免疫组织化学结果显示PTEN在200、100、50p^mol／LROS组中的表达显著高于0umol／L组（P〈0．01），VEGF—D在3组中的表达显著低于0p^mol／L组（P〈0．01）。两者在200、100、50umol／L组中的表达差异有统计学意义（P〈0．05）。Westernblot结果显示，用200、100、50、0umol／L的ROS干预后，PTEN／B-actin的灰度比分别为：1．47、1．06、0．77、0．49；VEGF—D／B-actin灰度比分别为：0．67、0．94、1．35、1．79，两者在4组中的表达差异有统计学意义（P〈0．01）。ROS能缩小裸鼠瘤体体积，提高抑瘤率，并呈剂量依赖性，差异有统计学意义（P〈0．01）。结论ROS活化后的PPAR-y1能抑制VEGF-D的表达，其机制可能与上调PTEN表达有关。

Objective To investigate the regulatory effect of activated peroxisome proliferator-acti- vated receptor-y （PPAR-y） on vascular endothelial growth factor-D （VEGF-D） expression and its possible mechanism. Methods The expression of phosphatase and tensin homolog deleted on chromosome ten （PTEN） and VEGF-D was detected by using immunohistochemistry and Western blotting in gastric cancer cell line BGC-823 which had been intervened with 200, 100, 50 and 0 Ixmol/L concentrations of rosiglita- zone （ROS） for 48 h. Xenograft tumor models were established by inoculating the intervened cells into the nude mice subcutaneously. The PTEN and VEGF-D expression levels were detected by using immunohisto- chemistry in tumor tissues of nude mice. Results The expression level of PTEN in 200, 100 and 50 pumol/L ROS groups was significantly higher, and that of VEGF-D was lower than in 0 umol/L group （P 〈0. 01 ） in tumor tisses of mice （P 〈 O. O1 ）. There was significant difference in the expression of PTEN and VEGF-D among 200, 100 and 50 Ixmol/L ROS groups （P 〈 O. 05 ）. Western blotting revealed the gray scale rate of PTEN/13-actin was 1.47, 1.06, 0.77 and 0.49, and that of VEGF-D/13-actin was 0.67, 0.94, 1.35 and 1.79 in the cells intervened with 200, 100, 50 and 0 Ixmol/L ROS, respectively. The expression of PT＇EN and VEGF-D had significant difference （P 〈 O. 01 ）. ROS could significantly and dose-dependently decrease the tumor volume and increase the tumor inhibition rate in the nude mice （P 〈 0. 01 ）. Conclusion The activated PPAR-y/ can suppress VEGF-D expression, which may be related to the up-regulation of PTEN gene expression.