Pioglitazone, a ligand for peroxisome proliferator-activated receptor-γ acts as an inhibitor of colon cancer liver metastasis

Shota Takano, Tetsuro Kubota, Hideki Nishibori, Hirotoshi Hasegawa, Yoshiyuki Ishii, Nobuhiro Nitori, Hiroki Ochiai, Koji Okabayashi, Yuko Kitagawa, Masahiko Watanabe, Masaki Kitajima

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the steroid receptor superfamily. Liganded PPARγ 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 PPARγ, 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 PPARγ expression in the HT-29 cells was evaluated. Results: Cultured HT-29 and SW480 cells expressed PPARγ 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 PPARγ a candidate target for the treatment/prevention of colon cancer metastasis.

Original languageEnglish
Pages (from-to)3593-3599
Number of pages7
JournalAnticancer research
Volume28
Issue number6 A
Publication statusPublished - 2008 Nov 1

Keywords

  • Colon cancer
  • Liver metastasis
  • Pioglitazone

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Takano, S., Kubota, T., Nishibori, H., Hasegawa, H., Ishii, Y., Nitori, N., Ochiai, H., Okabayashi, K., Kitagawa, Y., Watanabe, M., & Kitajima, M. (2008). Pioglitazone, a ligand for peroxisome proliferator-activated receptor-γ acts as an inhibitor of colon cancer liver metastasis. Anticancer research, 28(6 A), 3593-3599.