rosiglitazone and as601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells罗格列酮和as601245减少细胞粘附和迁移通过调制的特定基因表达在人类结肠癌细胞.pdfVIP
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rosiglitazone and as601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells罗格列酮和as601245减少细胞粘附和迁移通过调制的特定基因表达在人类结肠癌细胞
Rosiglitazone and AS601245 Decrease Cell Adhesion and
Migration through Modulation of Specific Gene
Expression in Human Colon Cancer Cells
1. 2. 3 2 2
Angelo Cerbone , Cristina Toaldo , Rosalba Minelli , Eric Ciamporcero , Stefania Pizzimenti ,
2 1 2 2 3
Piergiorgio Pettazzoni , Guglielmo Roma , Mario Umberto Dianzani , Chiara Ullio , Carlo Ferretti ,
3 2
Chiara Dianzani , Giuseppina Barrera *
1 MerckSerono Ivrea – RBM S.p.A., Istituto di Ricerche Biomediche A. Marxer, Colleretto Giacosa, Turin, Italy, 2 Section of General Pathology, Department of Medicine and
Experimental Oncology, University of Turin, Turin, Italy, 3 Department of Science and Pharmaceutical Technology, University of Turin, Turin, Italy
Abstract
PPARs are nuclear receptors activated by ligands. Activation of PPARc leads to a reduction of adhesion and motility in some
cancer models. PPARc transcriptional activity can be negatively regulated by JNK-mediated phosphorylation. We postulated
that the use of agents able to inhibit JNK activity could increase the effectiveness of PPARc ligands. We analysed the effects
of rosiglitazone (PPARc ligand) and AS601245 (a selective JNK inhibitor) alone or in association on adhesion and migration
of CaCo-2, HT29, and SW480 human colon cancer cells and investigated, through microarray analysis, the genes involved in
these processes. Cell adhesion and migration was strongly inhibited by rosiglitazone and AS601245. Combined treatment
with the two compounds resulted in a greater reduction of the adhesion and migration capacity
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