Pioglitazone, a Ligand for Peroxisome Proliferator-activated Receptor-γ Acts as an Inhibitor of Colon Cancer Liver Metastasis

Background: Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a member of the steroid receptor superfamily. Liganded PPAR gamma can inhibit cancer cell proliferation. The in vitro and in vivo inhibitory effect of the synthetic ligands, ciglitazone (CGZ) and pioglitazone (PGZ), on human colon cancer was investigated. Materials and Methods: Cell proliferation and the expression of PPAR gamma, cyclooxygenase (COX)-2 and cyclin D1 were assessed in colon cancer cells treated with CGZ or PGZ. After subcutaneous or splenic inoculation of severe combined immunodeficient (SCID) mice using colon cancer HT-29 and SW480 cells, PGZ was administered orally and tumor growth inhibition was assessed by xenograft volume. The COX-2, cyclin D1 and PPAR gamma expression in the HT-29 cells was evaluated. Results: Cultured HT-29 and SW480 cells expressed PPAR gamma and proliferation was inhibited by CGZ and PGZ. Oral PGZ inhibited xenograft tumor growth and liver metastases in the SCID mouse and suppressed expression of COX-2 and cyclin D1 in HT-29 cells. Conclusion: PGZ down-regulates COX-2 and cyclin D1 and inhibits colon cancer proliferation and liver metastasis, making PPAR gamma a candidate target for the treatment/prevention of colon cancer metastasis.