Rosiglitazone and AS601245 decrease cell adhesion and migration through modulation of specific gene expression in

Angelo Cerbone1, Cristina Toaldo, Rosalba Minelli

  • 1MerckSerono Ivrea - RBM SpA, Istituto di Ricerche Biomediche A Marxer, Colleretto Giacosa, Turin, Italy.

Plos One
|July 5, 2012
PubMed

Insights

Combining a PPARγ ligand with a JNK inhibitor significantly reduces colon cancer cell adhesion and migration. This synergistic effect involves down-regulation of β-PIX, a key protein in cell migration processes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors.
  • PPARγ activation reduces cancer cell adhesion and motility.
  • JNK-mediated phosphorylation negatively regulates PPARγ activity.

Purpose of the Study:

  • To investigate if inhibiting JNK activity enhances PPARγ ligand effectiveness.
  • To analyze the combined effects of a PPARγ ligand and a JNK inhibitor on colon cancer cell adhesion and migration.
  • To identify genes involved in these cellular processes.

Main Methods:

  • Utilized rosiglitazone (PPARγ ligand) and AS601245 (JNK inhibitor) on colon cancer cell lines (CaCo-2, HT29, SW480).
  • Assessed cell adhesion and migration.
  • Performed microarray analysis to identify gene expression changes.
  • Conducted Western blot analysis and gene transfection experiments.

Main Results:

  • Both rosiglitazone and AS601245 individually inhibited cell adhesion and migration.
  • Combined treatment showed a greater reduction in adhesion and migration.
  • Down-regulation of fibrinogen chains and release was observed.
  • Combined treatment significantly down-regulated ARHGEF7/β-PIX gene and protein.
  • β-PIX gene transfection abrogated the inhibitory effects of the treatments on cell migration.

Conclusions:

  • Combined PPARγ ligand and JNK inhibitor treatment enhances the inhibition of colon cancer cell migration.
  • β-PIX protein plays a crucial role in mediating the anti-migratory effects.
  • This highlights a synergistic interaction between PPARγ ligands and anti-inflammatory agents for cancer therapy.

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