Background and aims: Data regarding the effect of peroxisome proliferator-activated receptor γ (PPAR-γ) ligands on the invasive ability of colon cancer cells are currently limited. This study was designed to examine the effects of PPAR-γ agonists on the proliferation and invasion of two colon cancer cells to identify the role of PPAR-γ in colon cancer growth and metastasis.
Methods: SW480 and LS174T cells were treated with PPAR-γ ligands, pioglitazone and 15-deoxy-δ(12,14)-prostaglandin J2 (15d-PGJ2), as well as their combinations with the PPAR-γ antagonist GW9662. MTT assay was used to determine the antiproliferative effects. Cell cycle analysis was conducted by flow cytometry. The mRNA and protein expression were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively. The invasive ability of cells was determined by the BD BioCoat Matrige invasion chamber.
Results: Pioglitazone and 15d-PGJ2 inhibited the proliferation of both colon cancer cell lines in a dose-dependent manner. This growth inhibitory effect was reversed by GW9662. Results from flow cytometry demonstrated G1 arrest following treatment with pioglitazone and 15d-PGJ2. The expression of matrix metalloproteinase-7 (MMP-7) was only detected in LS174T cells, while its tissue inhibitor-1 (TIMP-1) was expressed in both colon cancer cells. 15d-PGJ2 and pioglitazone downregulated MMP-7 expression and upregulated TIMP-1 expression. PPAR-γ agonists can only inhibit invasive activity of LS174T cells.
Conclusions: PPAR-γ agonists have inhibitory effects on the proliferation of colon cancer cell lines associated with G1 cell cycle arrest and invasive activity. The latter effect is demonstrated in certain cell lines through the down-regulation of MMP-7 synthesis.
- 15d-PGJ2, 15-deoxy-δ(12,14)-prostaglandin J2
- DMSO, dimethyl sulfoxide
- ELISA, enzyme-linked immunosorbent assay
- MMP-7, matrix metalloproteinase-7
- OD, optical density
- PI, propidium iodide
- PPAR-γ, peroxisome proliferator-activated receptor γ
- PVDF, polyvinylidene difluoride
- RT-PCR, reverse transcriptase polymerase chain reaction
- SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- TIMP-1, tissue inhibitor-1
- TZD, thiazolidinedione
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