Pioglitazone, a ligand for peroxisome proliferator-activated receptor-gamma acts as an inhibitor of colon cancer liver metastasis.
Year: 2008
Type: article
Abstract: BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a member of the steroid receptor superfamily. Liganded PPARgamma 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 PPARgamma, 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 PPARgamma expression in the HT-29 cells was evaluated. RESULTS: Cultured HT-29 and SW480 cells expressed PPARgamma 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 PPARgamma a candidate target for the treatment/prevention of colon cancer metastasis.
Source: PubMed
Institutions: Keio University, Keio University Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1879008530