Document Detail


Rapamycin inhibits growth of cholangiocarcinoma cells.
MedLine Citation:
PMID:  19453019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: The immunosuppressive agent rapamycin is currently being evaluated for its antineoplastic effect. In the present study, the antineoplastic effect of rapamycin against cholangiocarcinoma was studied in vitro. METHODOLOGY: To explore the therapeutic potential of rapamycin, expression of mTOR in four cholangiocarcinoma cell lines--TFK1, HuCCT1, NOZW, and OZ--was evaluated by real-time PCR. The cell lines were then cultured with rapamycin (200 nM), and changes in the expression of Akt, phosphorylated PTEN (pPTEN), and phosphorylated S6 (pS6) were evaluated by western blotting. Finally, the cell lines were cultured with rapamycin (0, 25, 50, 100, 200 nM), gemcitabine (0, 0.5, 1, 2 microM), or both, and the antiproliferative effect was evaluated by MTT assay. RESULTS: All four cholangiocarcinoma cell lines expressed endogenous mTOR-mRNA, the of expression being highest in HuCCT1 (65.8) and lowest in TFK1 (17.6). Western blotting revealed that rapamycin treatment decreased Akt expression significantly in all four cell lines (TFK1; 15.5%, HuCCT1; 6.3%, NOZW; 9.8%, OZ; 19.5%), and also decreased the expression of p-PTEN (TFK1; 10.6%, HuCCT1; 5.4%, NOZ-W; 12.2%, OZ; 12.2%) and pS6 (TFK1; 64.0%, HuCCT1; 73.9%, NOZW; 78.6%, OZ; 47.6%) in all four cell lines. Finally, rapamycin significantly inhibited the growth of all four cell lines in a dose-dependent manner. Gemcitabine inhibited the growth of NOZW and HuCCT1, but its effect was less marked on TFK1 and OZ. Furthermore, a synergistic anti-proliferative effect of rapamycin and gemcitabine was observed in TFK1, NOZW, and OZ, but not in HuCCT1. CONCLUSION: Rapamycin effectively inhibited the growth of the four cholangiocarcinoma cell lines tested, and a synergistic effect with gemcitabine was observed in three of them. Rapamycin offers a new therapeutic strategy to inhibit the growth of cholangiocarcinoma.
Authors:
Toshie Okada; Tokihiko Sawada; Keiichi Kubota
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Hepato-gastroenterology     Volume:  56     ISSN:  0172-6390     ISO Abbreviation:  Hepatogastroenterology     Publication Date:    2009 Jan-Feb
Date Detail:
Created Date:  2009-05-20     Completed Date:  2009-06-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8007849     Medline TA:  Hepatogastroenterology     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  6-10     Citation Subset:  IM    
Affiliation:
Second Department of Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / pharmacology*
Blotting, Western
Cell Line, Tumor / drug effects,  metabolism
Cholangiocarcinoma / drug therapy*
Dose-Response Relationship, Drug
Humans
PTEN Phosphohydrolase / metabolism
Phosphorylation
Protein Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Sirolimus / pharmacology*
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 53123-88-9/Sirolimus; EC 2.7.-/Protein Kinases; EC 2.7.1.-/mTOR protein; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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