Regulation of angiogenesis by peroxisome proliferator-activated receptor-?in pancreatic carcinoma and its possible mechanisms
- VernacularTitle:过氧化物酶增殖物活化受体-?在胰腺癌新生血管生成中的调节作用及其可能机制
- Author:
Yuwei DONG
;
Xingpeng WANG
;
Kai WU
;
Al ET
;
- Publication Type:Journal Article
- Keywords:
Peroxisome proliferator-activated receptor-?;
Angiogenesis;
Vascular endothelial growth factor;
Pancreatic carcinoma
- From:
Chinese Journal of Digestion
1996;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of peroxisome proliferator activated receptor ?(PPAR ?) in angiogenesis in human pancreatic carcinoma with reference to the regulation of vascular endothelial growth factor (VEGF). Methods Expression of PPAR ? 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 ? and, 9 cis retinoic acid(9 cis RA) the ligand of retinoic X receptor(RXR)?, at different concentrations and durations, was detected by semi quantitative RT PCR. Effects of Rosiglitazone, a selective PPAR ? 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 ?mol?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 ? 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