Ohigashi T
Department of Urology, School of Medicine, Keio University, Tokyo, Japan.
Keio J Med. 1990 Dec;39(4):254-60. doi: 10.2302/kjm.39.254.
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.
设计用于刺激处于活跃细胞周期的癌细胞的策略可能会提高诸如甲氨蝶呤等S期特异性抗癌药物的疗效。在本研究中，体外研究了粒细胞集落刺激因子（G-CSF）对培养的人膀胱癌细胞增殖以及抗癌药物对膀胱癌细胞细胞毒性的影响。培养的人膀胱癌细胞KU-1和NBT-2经10 ng/ml G-CSF处理24小时和48小时后，其3H-胸腺嘧啶核苷摄取量显著高于未用G-CSF处理的细胞。然而，10 ng/ml G-CSF处理72小时对KU-1和NBT-2的细胞数量没有显著影响。125I标记的G-CSF突变体KW-2228与KU-1和NBT-2的结合受到未标记的KW-2228浓度依赖性抑制，这表明两种细胞上均存在G-CSF受体。Scatchard分析表明，KU-1和NBT-2的受体密度分别为每细胞1770个和3070个。与单独使用甲氨蝶呤治疗相比，甲氨蝶呤与G-CSF联合治疗导致细胞毒性作用显著增加。本研究支持甲氨蝶呤与G-CSF联合治疗可提高晚期膀胱癌临床反应的可能性。
