过氧化酶增殖因子活化受体对胃癌组织中血管内皮生长因子C的调节作用

摘要

目的:探讨过氧化酶增殖因子活化受体(peroxisome proliferator-activated receptor gamma,PPARγ)和血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C)在胃癌组织中的表达及其相关性.研究PPARγ受体激动剂罗格列酮(rosiglitazone,ROS)对VEGF-C的调节作用.方法:选取经病理证实为胃癌的手术切除石蜡标本60例,同时选取相同病例的癌旁组织,癌旁正常组织作为对照,采用免疫组化法检测PPARγ和VEGF-C表达,分析其与临床病理特征的关系.采用免疫印迹法观察不同浓度的罗格列酮作用于MKN-45 胃癌细胞48h时VEGF-C 蛋白表达的变化.结果:免疫组化提示PPARγ阳 性率在胃癌中是68.33%,癌旁组织中是51.67%,癌旁正常组织中是20%,三者表达差异有统计学意义(P=0.00);VEGF-C阳性率在胃癌中是63.33%,癌旁组织中是45%,癌旁正常组织中是23.33%,三者表达差异有统计学意义(P=0.00);PPARγ 的蛋白表达与VEGF-C表达为负相关(r=-0.897,P=0.000);2者的表达均与胃癌淋巴结转移及TNM分期有关(均P<0.05).West-blot结果提示选择12.5μmol/L,25μmol/L,50μmol/L,100μmol/L四个浓度的ROS,VEGF-C/β-actin灰度比分别为:0.42,0.35,0.33,0.32,抑制率分别为:57.8%,64.6%,66.6%,68%,对VEGF-C蛋白表达差别具有统计学意义,(P＝0.000).随着PPARγ配体浓度的增加,对VEGF-C的抑制作用增强.β-actin表达在各组中无明显差异.结论:胃癌组织中PPARγ和VEGF-C呈高表达,联合检测这2个指标对评估胃癌浸润转移及判断病情、监测预后有重要意义.PPARγ可能通过抑制VEGF-C 的表达而阻止胃癌的淋巴转移.%Objective :To investigate the significance of expression of peroxisome proliferator - activated receptor gamma( PPARγ ) and vascular endothelial growth factor - C ( VEGF - C ) in gastric carcinoma as well as their correlation. To study regulation of rosiglitazone( ROS ) to VEGF - C. Methods: The tissue chips of 60 cases of gastric cancer tissues were adopted by the immunohistochemistry compared with paired adjacent mucosa and normal mucosa from 60 same cases, the expression of PPARγ and VEGF - C were detected by S - P, the clinical characteristics were analyzed. Protein expression of VEGF - C was studied with ROS of different density to gastric cancer cell MKN - 45 in 48h by western - blot. Results: The positive rate of PPARγ protein was significantly higher in gastric carcinoma 68. 33％ ( 60 cases ) than in their paired adjacent mucosa 51. 67％ ( 60 cases ) and normal mucosa 20％ ( 60 cases ); The positive rate of VEGF - C protein was 63. 33％ ,45％ and 23. 33％ respectively ( P =0. 00 ); PPARγ expression was negatively correlated with VEGF - C ( r = - 0. 897 ,P =0. 000 )in protein levees. There were significant associations between the expression of these proteins and lymph node metastasis, and TNM staging ( all P ＜ 0. 05 ). The gray scale rates of VEGF - C/β - actin were 0. 42 ,0. 35 ,0. 33 and 0. 32 , the inhibition rates were 57. 8％ , 64.6％ ,66.6％ and 68％ respectively. The differences of protein expression used ROS 12. 5μmol/L, 25μmol/L, 50μmol/L and 100μmol/L was significant by western - blot ( P =0. 000 ). Inhihition of ROS to VEGF - C was reinforce accompany with raise of ROS density, while the expression of β - actin was uniform. Conclusion : PPARγ and VEGF - C expression are high in gastric cancer tissues, there are not relationship in PPARγ and VEGF - C, combined testing of these two markers is important in the evaluation of tumor metastasis and invasion, and is helpful in the prediction of the prognosis. PPARγ maybe affect lymph node metastasis of gastric cancer through restraining the VEGF - C expression.