Effect of ligand troglitazone on peroxisome proliferator-activated receptor gamma expression and cellular growth in human colon cancer cells.
OBJECTIVE
To investigate the effect of troglitazone on pe-roxisome proliferator-activated receptor gamma (PPARgamma) expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.


METHODS
Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to detect the effect of troglitazone on PPARgamma expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosis-related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively.


RESULTS
The expression of PPARgamma in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21(WAF1/CIP1) (p21), p27(KIP1) (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells.


CONCLUSIONS
Troglitazone is an inductor of PPARgamma in colon cancer cells and inhibits PPARgamma-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53-dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.
Ming
Mei
M
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Yu
Jie-Ping
JP
Meng
Xiang-Zhi
XZ
Zhou
Yan-Hong
YH
Yu
Hong-Gang
HG
Luo
He-Sheng
HS
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002839:Chromans / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077288:Troglitazone