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, Yuukou Kitagawa, Masahiko Watanabe, Masaki Kitajima

Research output: Contribution to journalArticle

35 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

Fingerprint

pioglitazone
Peroxisome Proliferator-Activated Receptors
Liver Neoplasms
Colonic Neoplasms
HT29 Cells
Cyclin D1
Cyclooxygenase 2
Neoplasm Metastasis
Ligands
SCID Mice
Heterografts
Cell Proliferation
Neoplasms
Steroid Receptors
Growth
Cultured Cells
Down-Regulation

Keywords

  • Colon cancer
  • Liver metastasis
  • Pioglitazone

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Takano, S., Kubota, T., Nishibori, H., Hasegawa, H., Ishii, Y., Nitori, N., ... 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.

Pioglitazone, a ligand for peroxisome proliferator-activated receptor-γ acts as an inhibitor of colon cancer liver metastasis. / Takano, Shota; Kubota, Tetsuro; Nishibori, Hideki; Hasegawa, Hirotoshi; Ishii, Yoshiyuki; Nitori, Nobuhiro; Ochiai, Hiroki; Okabayashi, Koji; Kitagawa, Yuukou; Watanabe, Masahiko; Kitajima, Masaki.

In: Anticancer Research, Vol. 28, No. 6 A, 11.2008, p. 3593-3599.

Research output: Contribution to journalArticle

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, vol. 28, no. 6 A, pp. 3593-3599.
Takano S, Kubota T, Nishibori H, Hasegawa H, Ishii Y, Nitori N et al. Pioglitazone, a ligand for peroxisome proliferator-activated receptor-γ acts as an inhibitor of colon cancer liver metastasis. Anticancer Research. 2008 Nov;28(6 A):3593-3599.
Takano, Shota ; Kubota, Tetsuro ; Nishibori, Hideki ; Hasegawa, Hirotoshi ; Ishii, Yoshiyuki ; Nitori, Nobuhiro ; Ochiai, Hiroki ; Okabayashi, Koji ; Kitagawa, Yuukou ; Watanabe, Masahiko ; Kitajima, Masaki. / Pioglitazone, a ligand for peroxisome proliferator-activated receptor-γ acts as an inhibitor of colon cancer liver metastasis. In: Anticancer Research. 2008 ; Vol. 28, No. 6 A. pp. 3593-3599.
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