gw-501516 and Intestinal-Polyps

gw-501516 has been researched along with Intestinal-Polyps* in 2 studies

Other Studies

2 other study(ies) available for gw-501516 and Intestinal-Polyps

Article	Year
Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. Proceedings of the National Academy of Sciences of the United States of America, 2006, Dec-12, Volume: 103, Issue:50 Peroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes. However, PPARdelta's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARdelta decreases intestinal adenoma growth in Apc(Min/+) mice and inhibits tumor-promoting effects of a PPARdelta agonist GW501516. More importantly, we found that activation of PPARdelta up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARdelta agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer. Topics: Adenoma; Animals; Cell Line, Tumor; Cell Survival; Disease Progression; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Humans; Intestinal Neoplasms; Intestinal Polyps; Male; Mice; Mice, Knockout; PPAR delta; Proto-Oncogene Proteins c-akt; Thiazoles; Vascular Endothelial Growth Factor A	2006
Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nature medicine, 2004, Volume: 10, Issue:3 We treated Apc(min) mice, which are predisposed to intestinal polyposis, with a selective synthetic agonist of peroxisome proliferator-activated receptor-delta (PPAR-delta). Exposure of Apc(min) mice to the PPAR-delta ligand GW501516 resulted in a significant increase in the number and size of intestinal polyps. The most prominent effect was on polyp size; mice treated with the PPAR-delta activator had a fivefold increase in the number of polyps larger than 2 mm. Our results implicate PPAR-delta in the regulation of intestinal adenoma growth. Topics: Adenoma; Adenomatous Polyposis Coli Protein; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Genes, APC; Humans; Intestinal Neoplasms; Intestinal Polyps; Ligands; Mice; Receptors, Cytoplasmic and Nuclear; Thiazoles; Transcription Factors	2004

Article

Year

Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression.

Proceedings of the National Academy of Sciences of the United States of America, 2006, Dec-12, Volume: 103, Issue:50

Peroxisome proliferator-activated receptor (PPAR) delta is a member of the nuclear hormone receptor superfamily. PPARdelta may ameliorate metabolic diseases such as obesity and diabetes. However, PPARdelta's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARdelta decreases intestinal adenoma growth in Apc(Min/+) mice and inhibits tumor-promoting effects of a PPARdelta agonist GW501516. More importantly, we found that activation of PPARdelta up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARdelta agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARdelta antagonists for prevention and/or treatment of cancer.

Topics: Adenoma; Animals; Cell Line, Tumor; Cell Survival; Disease Progression; Enzyme Activation; Female; Gene Expression Regulation, Neoplastic; Humans; Intestinal Neoplasms; Intestinal Polyps; Male; Mice; Mice, Knockout; PPAR delta; Proto-Oncogene Proteins c-akt; Thiazoles; Vascular Endothelial Growth Factor A

2006

Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth.

Nature medicine, 2004, Volume: 10, Issue:3

We treated Apc(min) mice, which are predisposed to intestinal polyposis, with a selective synthetic agonist of peroxisome proliferator-activated receptor-delta (PPAR-delta). Exposure of Apc(min) mice to the PPAR-delta ligand GW501516 resulted in a significant increase in the number and size of intestinal polyps. The most prominent effect was on polyp size; mice treated with the PPAR-delta activator had a fivefold increase in the number of polyps larger than 2 mm. Our results implicate PPAR-delta in the regulation of intestinal adenoma growth.

Topics: Adenoma; Adenomatous Polyposis Coli Protein; Animals; Cell Line, Tumor; Dose-Response Relationship, Drug; Genes, APC; Humans; Intestinal Neoplasms; Intestinal Polyps; Ligands; Mice; Receptors, Cytoplasmic and Nuclear; Thiazoles; Transcription Factors

2004