AIM: To investigate the effect of troglitazone on pe- roxisome proliferator-activated receptor γ (PPARγ) expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molec...AIM: To investigate the effect of troglitazone on pe- roxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by ? ow cytometry. Apoptosis- related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively. RESULTS: The expression of PPARγ 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 p21WAF1/CIP1 (p21), p27KIP1 (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells. CONCLUSION: Troglitazone is an inductor of PPARγin colon cancer cells and inhibits PPARγ-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.展开更多
文摘AIM: To investigate the effect of troglitazone on pe- roxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by ? ow cytometry. Apoptosis- related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively. RESULTS: The expression of PPARγ 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 p21WAF1/CIP1 (p21), p27KIP1 (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells. CONCLUSION: Troglitazone is an inductor of PPARγin colon cancer cells and inhibits PPARγ-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.
