Granulocyte-colony stimulating factor enhances the cytotoxic effects of methotrexate to bladder cancer cells in vitro.
It is possible that a strategy designed to stimulate cancer cells in the active cell cycle may increase the effectiveness of S-phase specific anti-cancer agents such as methotrexate. In this study, the effects of granulocyte-colony stimulating factor (G-CSF) on the proliferation of cultured human bladder cancer cells and on the cytotoxicity of anti-cancer drugs to bladder cancer cells were studied in vitro. The 3H-thymidine uptake of cultured human bladder cancer cells, KU-1 and NBT-2, was significantly higher when the cells were treated with 10 ng/ml G-CSF than without G-CSF after 24- and 48-hour incubation. However, the cell numbers of KU-1 and NBT-2 were not significantly affected by 72-hour treatment with 10 ng/ml G-CSF. The binding of 125I-labeled KW-2228, a muteins of G-CSF, to KU-1 and NBT-2 was inhibited by unlabeled KW-2228 in a concentration dependent manner, which demonstrated the presence of G-CSF receptors on both cells. Scatchard analysis showed that the receptor densities of KU-1 and NBT-2 were 1770 and 3070 per cell, respectively. The combination treatment with methotrexate and G-CSF resulted in a significant increase in cytotoxic effects, when compared with methotrexate treatment alone. This study supports the possibility that the combination therapy of methotrexate and G-CSF increases clinical response in the treatment of advanced bladder cancer.
Ohigashi
T
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Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D008727:Methotrexate