Imatinib mesylate (STI571; Glivec)—a new approach in the treatment of biliary tract cancer?
作者:
Marcus Wiedmann,
Florian Kreth,
Jürgen Feisthammel,
Michael Deininger,
Joachim Mössner,
Karel Caca,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 9
页码: 751-760
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: biliary tract cancer;cholangiocarcinoma;tyrosine kinase inhibitor
数据来源: OVID
摘要:
Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kitand platelet-derived growth factor (PDGF) receptors (PDGFRs) and the effects of the tyrosine kinase inhibitor imatinib±5-fluorouracil (5-FU) on proliferation and apoptosis in biliary tract cancer cell lines. The expression of c-kitand PDGFR mRNA was examined in 12 biliary tract cancer cell lines using RT-PCR. Cells were treated with imatinib (1, 10, 20 and 50 μmol/l)±5-FU (0.1 μg/ml) for 6 days and inhibition of cell growth was assessed by manual cell counting. Cell proliferation and apoptosis were analyzed by flow cytometry of BrdU and Annexin-V/propidium iodide-stained cells. c-kitand PDGF mRNA expression was detected in 50 and 75%, respectively. Imatinib (10 and 20 μmol/l) alone inhibited cell growth significantly higher in c-kit+cell lines (p<0.02) and inhibition was independent of PDGFR status. The combination with 5-FU increased the effect of imatinib mesylate in all cell lines. Treatment of cells with imatinib±5-FU was associated with a significant induction of apoptosis, but no inhibition of proliferation. We conclude that imatinib alone exerts marked effects on c-kit+biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers.
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