摘要
目的 探讨过氧化物酶增殖物活化受体 γ(PPAR γ)对胰腺癌血管内皮细胞生长因子(VEGF)表达的调节作用 ,以及对胰腺癌新生血管生成的抑制作用 ,旨在进一步揭示PPAR γ抑制胰腺癌生长的机制。方法 体外培养胰腺癌细胞株SW 1990 ,给予PPAR γ配体 15 脱氧 前列腺素J2 (15d PGJ2 )及维甲类受体 (RXR)α配体 9 顺式 维甲酸 (9 cis RA) ,经不同浓度及不同时间作用后 ,用RT PCR方法检测其对SW 1990细胞VEGF表达的调节作用。建立裸鼠SW 1990细胞移植瘤 ,分为对照组和罗格列酮组各 15只 ,将罗格列酮配成 10 μmol·kg-1·d-1予治疗组饮用。采用半定量RT PCR方法检测PPAR γ激动剂罗格列酮对裸鼠移植瘤组织VEGF表达的影响。应用免疫组化染色标记移植瘤新生血管壁Ⅳ型胶原 ,计算肿瘤组织微血管密度 (MVD)。结果 RT PCR及免疫细胞化学结果显示SW 1990细胞系存在PPAR γmRNA和蛋白的表达。RT PCR揭示 ,随着 15d PGJ2 、9 cis RA及其联合作用浓度的提高以及作用时间的延长 ,SW 1990细胞分泌的VEGF受到抑制 ,且呈时间和剂量依赖性。在裸鼠移植瘤的体内实验中 ,对照组肿瘤组织MVD为 31.4 4± 6 .0 6 ,罗格列酮处理组为 10 .6 7± 3.0 7,两组间差异有显著性 (P <0 .0 1)。半定量RT
Objective To explore the role of peroxisome proliferator activated receptor γ(PPAR γ) in angiogenesis in human pancreatic carcinoma with reference to the regulation of vascular endothelial growth factor (VEGF). Methods Expression of PPAR γ in SW1990 pancreatic carcinoma cells was examined by RT PCR and immunocytochemical staining. Secretion of VEGF by SW1990 cells, treated by 15 deoxy delta(12,14) prostaglandin J 2(15d PGJ 2), the ligand of PPAR γ and, 9 cis retinoic acid(9 cis RA) the ligand of retinoic X receptor(RXR)α, at different concentrations and durations, was detected by semi quantitative RT PCR. Effects of Rosiglitazone, a selective PPAR γ activator, on the changes of microvascular density (MVD) and VEGF expression were investigated in 30 SW1990 cell xenografted nude mice, among which 15 were in the treatment group (drank a solution of Rosiglitazone at the dose of 10 μmol·kg -1 ·d -1 ) and 15 in the control group. Neovasculature was detected using immunohistochemistry staining labeled with anti Ⅳ collagen antibody and indicated by MVD. Results RT PCR and immunocytochemical staining showed that PPAR γ mRNA and protein were expressed in the SW1990 cell line. Semi quantitative RT PCR demonstrated that the combination of 15d PGJ 2 and 9 cis RA had a potent inhibitory effect on the expression of VEGF in SW1990 cells in both dose and time dependent manners. In vivo study, the MVD was statistically decreased in Rosiglitazone treated mice (10.67±3.07) compared with that in the control group (31.44±6.06) ( P <0.01). VEGF expression in xenograft tumor tissues determined by semi quantitative RT PCR was also markedly down regulated in Rosiglitazone treated mice. Conclusions Activation of PPAR γ suppresses angiogenesis in pancreatic carcinoma. This action is probably associated with the down regulation of angiogenic factor, VEGF, which may be modulated by PPAR γ. These results suggest that PPAR γ might be a novel molecular therapeutic target
出处
《中华消化杂志》
CAS
CSCD
北大核心
2004年第5期293-296,共4页
Chinese Journal of Digestion
基金
上海市科技发展基金重点项目 (9941190 16)
