Hyperoxia-induced improvement of the in vitro response to gemcitabine in transitional cell carcinoma.

نویسندگان

  • Guido Fechner
  • Frank Dederichs
  • Doris Schmidt
  • Stefan Müller
  • Peter Vaupel
  • Peter Albers
چکیده

BACKGROUND Anemic tissue hypoxia can decrease the effects of chemotherapy in bladder cancer. Hypoxia leads to overexpression of hypoxia-inducible factor (HIF) and increased synthesis of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Tumor cell survival, invasion and angiogenesis thereby compromise treatment. MATERIALS AND METHODS Monolayer cultures of RT112, RT4, T24 and TCC SUP cells were incubated with or without gemcitabine and different gas mixtures (hypoxia, normoxia or hyperoxia). Cell proliferation (microculture tetrazolium assay), VEGF (enzyme-linked immunosorbent assay) and HIF-1alpha (Western blot analysis) were determined. RESULTS Hypoxia led to increased proliferation of transitional cell carcinoma (TCC) cells and elevated levels of HIF-1alpha and VEGF. Hyperoxia inhibited cell growth and lowered the concentration of VEGF. Treatment with gemcitabine was less effective under hypoxia. CONCLUSION Hypoxia enhances TCC growth and may intensify angiogenesis mediated by VEGF. Hypoxia compromises treatment with gemcitabine. Correction of anemia might provide advantages in chemotherapeutic strategies for TCC.

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عنوان ژورنال:
  • Anticancer research

دوره 25 5  شماره 

صفحات  -

تاریخ انتشار 2005