PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo

I. K. Choi, Yeul Hong Kim, Jun Suk Kim, Jae Hong Seo

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

PPAR-γ has been known to induce suppression, differentiation and reversal of malignant changes in colon cancer in vitro. However, there are several reports that PPAR-γ ligands enhance colon polyp development in APCmin mice in vivo. These contradictory results have not yet been thoroughly explained. To explain the contradictory results, we analyzed the effects of different concentrations of the PPAR-γ agonist, 15-deoxy-D12, 14-prostaglandin (15-d Δ PGJ2) and pioglitazone, on APC gene-mutated colon cancer cell lines (HT-29). We measured cell growth and suppression by cell count and MTT assay and analyzed the expression of β-catenin and c-Myc protein by Western blot. In addition, we inoculated HT-29 cells into APC min mice to compare tumor size. High concentrations (10-100 μM/L 15-d Δ PGJ2 and pioglitazone) of PPAR-γ ligand suppressed growth, while low concentrations (0.01-1 μM/L 15-d Δ PGJ2 and pioglitazone) of PPAR-γ ligand promoted growth. In particular, the effects of 0.1 μM/L 15-d Δ PGJ2 and pioglitazone on cell growth were statistically significant (P = 0.003, P = 0.001, respectively). Tumor growth was associated with an increase in β-catenin and c-Myc expression. The growth of xenograft tumors was greater in PPAR-γ ligand-treated mice than in control mice (control vs day 14: P = 0.024, control vs day 28: P = 0.007). The expression of β-catenin and c-Myc protein were also elevated in PPAR-γ-treated mouse tissues. PPAR-γ ligand can promote the growth of APC-mutated HT-29 colon cancer cells in vitro and in vivo. In addition, the tumor promoting effect seems to be associated with an increase in β-catenin and c-Myc expression. We think that well-controlled clinical trials should be conducted to confirm our results and to verify clinical applications.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalInvestigational New Drugs
Volume26
Issue number3
DOIs
Publication statusPublished - 2008 Jun 1

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Peroxisome Proliferator-Activated Receptors
pioglitazone
Colonic Neoplasms
Ligands
Catenins
Growth
Proto-Oncogene Proteins c-myc
Neoplasms
APC Genes
HT29 Cells
In Vitro Techniques
Controlled Clinical Trials
Polyps
Heterografts
Prostaglandins
Colon
Cell Count
Western Blotting
Cell Line
9-deoxy-delta-9-prostaglandin D2

Keywords

  • β-Catenin
  • APC-mutated
  • c-Myc
  • PPAR-γ ligand

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo. / Choi, I. K.; Kim, Yeul Hong; Kim, Jun Suk; Seo, Jae Hong.

In: Investigational New Drugs, Vol. 26, No. 3, 01.06.2008, p. 283-288.

Research output: Contribution to journalArticle

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