| 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 |
Related Documents
:
|
1718439 - Phenotypic heterogeneity in cultured skin fibroblasts from patients with disorders of p... 2066379 - Applications of immortalized cells in basic and clinical neurology. 183999 - Quantitative variations of three different lectin receptors as a function of establishm... 17102969 - Growth substrate induced functional changes elucidated by ftir and raman spectroscopy i... 6292119 - Epstein-barr virus induction by a serum factor: iv. ubiquitous occurrence of the factor... 9357969 - Stem cell factor suppresses apoptosis in neuroblastoma cell lines. 14606959 - The histone deacetylase inhibitor trichostatin a modulates cd4+ t cell responses. 19372739 - Daxx is a predominately nuclear protein that does not translocate to the cytoplasm in r... 2570139 - Functional activity of intestinal epithelium demonstrated by mrna in situ hybridization. |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Significance of repeated resection for recurrent intrahepatic cholangiocarcinoma.
Next Document: Early or delayed laparoscopic cholecystectomy in acute cholecystitis? Conclusions of a controlled tr...