A Ligand for peroxisome proliferator-activated receptor gamma inhibits human cholangiocarcinoma cell growth: potential molecular targeting strategy for cholangioma.
Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have an antitumor effect. The aim of this study was to clarify whether PPARgamma ligands could inhibit the growth of human cholangiocarcinoma cells. PPAR( expression in HuH-28 and HuCCT1 cells (intrahepatic bile duct carcinoma) was determined using the reverse transcription-polymerase chain reaction (RT-PCR). Expression of PPARgamma mRNA was detected in both cell lines. Activation of PPARgamma by troglitazone caused marked growth inhibition in a time- and dose-dependent manner. Troglitazone inhibited the growth of human cholangiocarcinoma cell lines by inducing apoptosis and by cell cycle regulation (G1 arrest), and this was associated with caspase 3 and caspase 9 activation. Thus, molecular targeting with troglitazone, a nuclear receptor ligand, may be a promising strategy for treating cholangiocarcinoma, although a delivery system needs to be established.
Kobuke
T
T
Department of General Medicine and Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. stazuma@hiroshima-u.ac.jp
Tazuma
S
S
Hyogo
H
H
Chayama
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000201:enzymology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000201:enzymology / Q000473:pathology*; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008967:Molecular Biology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D008024:Ligands; D047495:PPAR gamma; D012334:RNA, Neoplasm; D045162:Thiazolidinediones; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D000077288:Troglitazone; D000077205:Pioglitazone