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. 2008 Jun;26(3):283-8.
doi: 10.1007/s10637-007-9108-x. Epub 2007 Dec 27.

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

I K Choi  1 , Y H Kim, J S Kim, J H Seo
Affiliations

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

I K Choi et al. Invest New Drugs. 2008 Jun.

Abstract

PPAR-gamma has been known to induce suppression, differentiation and reversal of malignant changes in colon cancer in vitro. However, there are several reports that PPAR-gamma 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-gamma agonist, 15-deoxy-D12, 14-prostaglandin (15-d Delta 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 beta-catenin and c-Myc protein by Western blot. In addition, we inoculated HT-29 cells into APCmin mice to compare tumor size. High concentrations (10-100 microM/L 15-d Delta PGJ2 and pioglitazone) of PPAR-gamma ligand suppressed growth, while low concentrations (0.01-1 microM/L 15-d Delta PGJ2 and pioglitazone) of PPAR-gamma ligand promoted growth. In particular, the effects of 0.1 microM/L 15-d Delta PGJ2 and pioglitazone on cell growth were statistically significant (P = 0.003, P = 0.001, respectively). Tumor growth was associated with an increase in beta-catenin and c-Myc expression. The growth of xenograft tumors was greater in PPAR-gamma ligand-treated mice than in control mice (control vs day 14: P = 0.024, control vs day 28: P = 0.007). The expression of beta-catenin and c-Myc protein were also elevated in PPAR-gamma-treated mouse tissues. PPAR-gamma 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 beta-catenin and c-Myc expression. We think that well-controlled clinical trials should be conducted to confirm our results and to verify clinical applications.

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