A ligand for peroxisome proliferator-activated receptor γ inhibits human cholangiocarcinoma cell growth : Potential molecular targeting strategy for cholangioma

• Published in: Digestive diseases and sciences Vol. 51; no. 9; pp. 1650 - 1657
• Main Authors: KOBUKE, T, TAZUMA, S, HYOGO, H, CHAYAMA, K
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.09.2006
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Bile Duct Neoplasms - enzymology; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - enzymology; Bile Ducts, Intrahepatic - pathology; Biological and medical sciences; Caspase 3; Caspase 9; Caspases - metabolism; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation - drug effects; Cholangiocarcinoma - enzymology; Cholangiocarcinoma - pathology; Chromans - pharmacology; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Ligands; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Molecular Biology; PPAR gamma - genetics; PPAR gamma - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - metabolism; Thiazolidinediones - pharmacology; Tumors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Cell proliferation; Targeting; Ligand; Hepatic disease; Metabolic diseases; Malignant tumor; Biliary tract disease; Peroxisome proliferator; Peroxisome proliferator-activated receptor γ; Malignant cholangioma; Cell cycle; Gastroenterology; Digestive diseases; Apoptosis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-005-9064-2

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.