Peroxisome proliferator-activated receptor gamma agonists inhibit the proliferation and invasion of human colon cancer cells.
OBJECTIVE
Data regarding the effect of peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligands on the invasive ability of colon cancer cells are currently limited. This study was designed to examine the effects of PPAR-gamma agonists on the proliferation and invasion of two colon cancer cells to identify the role of PPAR-gamma in colon cancer growth and metastasis.


METHODS
SW480 and LS174T cells were treated with PPAR-gamma ligands, pioglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), as well as their combinations with the PPAR-gamma 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-gamma agonists can only inhibit invasive activity of LS174T cells.


CONCLUSIONS
PPAR-gamma 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.
Shen
Dan
D
Department 1 of Internal Medicine & Geriatrics, Zhongnan Hospital, Wuhan University, Wuhan, PR China.
Deng
Changsheng
C
Zhang
Ming
M
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020783:Matrix Metalloproteinase 7