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

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Summary

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 APCmin 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.

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This work was supported by a Korea University Grant, Ministry of Health and Welfare, Republic of Korea (01-PG3-PG6-01GN07-0004) and The Post-Brain Korea 21 Project.

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  1. Division of Medical Oncology, Department of Internal Medicine, Medical College, Korea University Guro Hospital, 80 Guro-dong, Guro-ku, Seoul, South Korea

    I.K. Choi, Y.H. Kim, J.S. Kim & J.H. Seo

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  1. I.K. Choi
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  2. Y.H. Kim
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  3. J.S. Kim
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Correspondence to J.H. Seo.

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Choi, I., Kim, Y., Kim, J. et al. PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo. Invest New Drugs 26, 283–288 (2008). https://doi.org/10.1007/s10637-007-9108-x

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  • DOI: https://doi.org/10.1007/s10637-007-9108-x

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