Abstract
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 PPARγ ligands, 15 deoxy-Δ12,14 prostaglandin 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. Conclusions. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 7-22 |
| Number of pages | 16 |
| Journal | International Journal of Gastrointestinal Cancer |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2002 |
Bibliographical note
Funding Information:The authors thank Tatsuo Uchida for assistance in performing the statistical analysis and Jell Hsieh and Xiaofu Wang for technical assistance. In addition, we wish to thank Eileen Figueroa and Karen Martin for assistance in manuscript preparation. This work was supported by grants from the National Institutes of Health (PO1 DK35608, RO1 DK48498, T32 DK07639). Richard T. Ethridge is a recipient of a National Alpha Omega Alpha Student Research Fellowship and a McLaughlin Fellowship Award.
Funding
The authors thank Tatsuo Uchida for assistance in performing the statistical analysis and Jell Hsieh and Xiaofu Wang for technical assistance. In addition, we wish to thank Eileen Figueroa and Karen Martin for assistance in manuscript preparation. This work was supported by grants from the National Institutes of Health (PO1 DK35608, RO1 DK48498, T32 DK07639). Richard T. Ethridge is a recipient of a National Alpha Omega Alpha Student Research Fellowship and a McLaughlin Fellowship Award.
| Funders | Funder number |
|---|---|
| National Alpha Omega Alpha Student Research Fellowship | |
| National Institutes of Health (NIH) | RO1 DK48498, PO1 DK35608 |
| National Institute of Diabetes and Digestive and Kidney Diseases | T32DK007639 |
Keywords
- Apoptosis
- Cell cycle
- Pancreatic cancer
- Peroxisome proliferator-activated receptor γ
- Tumor invasion
ASJC Scopus subject areas
- Oncology
- Endocrinology
- Gastroenterology
