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Open Access 01-12-2006 | Research

In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer

Authors: Samir A Saidi, Cathrine M Holland, D Stephen Charnock-Jones, Stephen K Smith

Published in: Molecular Cancer | Issue 1/2006

Abstract

Fenofibrate, an agonist of PPAR-alpha, in doses above 25 μM, inhibits proliferation and induces apoptosis in Ishikawa endometrial cancer cells. We show that these effects are potentiated by retinoic acid, an agonist of the retinoid-X-receptor. DNA content analysis shows that G₁/S phase progression through the cell cycle is inhibited. Independent Component Analysis of gene microarray experiments demonstrated downregulation of Cyclin D1 (CCND1) and associated changes in cell cycle gene expression. Expression of PPAR-alpha mRNA was reduced by >75% using RNA-interference but this resulted in only minor changes in biological effects. A nude mouse model of endometrial carcinoma was used to investigate the effect of fenofibrate in vivo but failed to show consistent inhibition of tumour growth.

Conclusion

The combination of fenofibrate and retinoic acid is a potent inhibitor of Ishikawa endometrial cancer cell growth in vitro.

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Title: In vitro and in vivo effects of the PPAR-alpha agonists fenofibrate and retinoic acid in endometrial cancer
Authors: Samir A Saidi
Cathrine M Holland
D Stephen Charnock-Jones
Stephen K Smith
Publication date: 01-12-2006
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2006
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-5-13

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