Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies.
Control of proliferating potential of myeloid leukemia cells during long-term treatment with vitamin D3 analogues and other differentiation inducers in combination with antileukemic drugs: in vitro and in vivo studies.
复制标题
维生素 D3 类似物和其他分化诱导剂与抗白血病药物联合长期治疗期间控制髓系白血病细胞的增殖潜力：体外和体内研究。
作者：
T. Kasukabe;Y. Honma;M. Hozumi;T. Suda;Y. Nishii
研究了长期培养过程中分化诱导剂对小鼠和人髓系白血病细胞生长的抑制作用，以改进分化诱导剂治疗髓系白血病的策略。当以恒定的时间和浓度乘积（20天480nM）检查典型分化诱导剂1α,25-二羟基维生素D3对小鼠骨髓性白血病M1细胞增殖的作用时，用24nM 1α,25-二羟基维生素D3连续治疗对于抑制细胞增殖最有效。 20天后，通过用24 nM 1 α,25-二羟基维生素D3连续处理，累积细胞数减少约3 X 10(5)倍。当用地塞米松连续处理 M1 细胞时，获得了类似的结果。在开始用 24 nM 1 α,25-二羟基维生素 D3 连续治疗后约 25 天，M1 细胞出现对 1 α,25-二羟基维生素 D3 的抗性。另一方面，当M1细胞连续用1α,25-二羟基维生素D3和非细胞毒性剂量的抗白血病药物（例如1-β-D-阿拉伯呋喃糖基胞嘧啶和道诺霉素）处理时，至少35天内没有出现耐药细胞。在人单核细胞样细胞系 U937 中观察到 1α,25-二羟基维生素 D3 和抗白血病药物对细胞增殖的类似作用。与单独使用任一药物治疗相比，同时使用 1α-羟基维生素 D3 和道诺霉素治疗的接种 M1 细胞的同基因 SL 小鼠的存活时间延长得更多。这些结果表明，用分化诱导剂和某些抗白血病药物持续治疗可能比单独用分化诱导剂治疗更有效。
Growth inhibition of murine and human myeloid leukemia cells by differentiation inducers during long-term culture was examined to improve the strategy for therapy of myeloid leukemia by differentiation inducers. When the effect of 1 alpha,25-dihydroxyvitamin D3, a typical differentiation inducer, on proliferation of mouse myeloid leukemia M1 cells was examined at a constant product of time and concentration (480 nM in 20 days), the continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3 was the most effective for inhibition of cell proliferation. After 20 days, the cumulative cell number was reduced about 3 X 10(5) times by continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. Similar results were obtained when M1 cells were treated continuously with dexamethasone. M1 cells resistant to 1 alpha,25-dihydroxyvitamin D3 appeared about 25 days after the start of continuous treatment with 24 nM 1 alpha,25-dihydroxyvitamin D3. On the other hand, when M1 cells were treated continuously with 1 alpha,25-dihydroxyvitamin D3 and noncytotoxic doses of antileukemic drugs such as 1-beta-D-arabinofuranosylcytosine and daunomycin, resistant cells did not appear for at least 35 days. A similar effect of 1 alpha,25-dihydroxyvitamin D3 and antileukemic drugs on cell proliferation was observed with the human monoblast-like cell line U937. The survival of syngeneic SL mice inoculated with M1 cells was prolonged more by treatment with both 1 alpha-hydroxyvitamin D3 and daunomycin than by treatment with either drug alone. These results suggest that continuous treatment with both differentiation inducers and certain antileukemic drugs may be more effective therapeutically than treatment with a differentiation inducer alone.
DOI：
10.1016/s0021-9258(18)32158-6
发表时间：
1983-07
期刊：
The Journal of biological chemistry
影响因子：
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作者：
N. Nicola;D. Metcalf;M. Matsumoto;G. Johnson
通讯作者：
N. Nicola;D. Metcalf;M. Matsumoto;G. Johnson