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Peroxisome proliferator-activated receptor γ ligand inhibits cell growth and invasion of human pancreatic cancer cells

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Summary

Background. Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in certain human cancers; ligand-induced PPARγ activation can result in growth inhibition and differentiation in these cells. However, the precise mechanism for the antiproliferative effect of PPARγ ligands is not entirely known.

Aim of Study. The purpose of this study was to examine the effect of PPARγ ligands on pancreatic cancer cell growth and invasiveness.

Methods. The effect of two PPARγligands, 15 deoxy-Δ12,14prostaglandin J2 (15d-PGJ2) and ciglitazone, on the growth of four human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, Panc-1, and L3.6) was assessed. Expression of cell-cycle and apoptotic-related proteins was measured. Finally, the effect of 15d-PGJ2 on pancreatic cancer cell invasiveness and matrix metalloproteinase expression was determined.

Results. Both 15d-PGJ2 and ciglitazone inhibited the growth of all four pancreatic cancer cell lines in a dose- and time-dependent fashion. Treatment of BxPC-3 cells with 15d-PGJ2 resulted in a time-dependent decrease in cyclin D1 expression associated with a concomitant induction of p21waf1 and p27kip1. In addition, 15d-PGJ2 treatment induced apoptosis through activation of caspase-8, -9, and -3. Moreover, pancreatic cancer cell invasiveness was significantly suppressed after treatment with a nontoxic dose of 15d-PGJ2, which was associated with a reduction of MMP-2 and MMP-9 protein levels and activity.

Conclusion. These results demonstrate that PPARγ ligands have the dual advantage of inhibiting pancreatic cancer cell growth while reducing the invasiveness of the tumor cells, suggesting a potential role for these agents in the adjuvant treatment of pancreatic cancer.

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  1. Department of Surgery, The University of Texas Medical Branch, 301 University Boulevard, 77555-0536, Galveston, TX

    Koji Hashimoto, Richard T. Ethridge & B. Mark Evers

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  1. Koji Hashimoto
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Correspondence to B. Mark Evers.

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Hashimoto, K., Ethridge, R.T. & Evers, B.M. Peroxisome proliferator-activated receptor γ ligand inhibits cell growth and invasion of human pancreatic cancer cells. Int J Gastrointest Canc 32, 7–22 (2002). https://doi.org/10.1385/IJGC:32:1:7

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