Kabaya K, Obuchi M, Kuwaki T, Shibuya K, Watanabe M, Nemoto K, Yoshida K, Kusaka M, Inoue T, Seki M
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd, Gunma, Japan.
Leuk Res. 1996 Jan;20(1):27-35. doi: 10.1016/0145-2126(95)00099-2.
We investigated the in vitro and in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the proliferation of two murine leukemic cell lines. The rhG-CSF stimulated leukemic colony formation of the promyelocytic leukemic cell line L-8801 in methylcellulose culture and increased the number of L-8801 cells in liquid culture. However, rhG-CSF treatment prolonged the median survival period of mice implanted with L-8801 cells and the emergence of the leukemic blast cells in peripheral blood. Meanwhile, rhG-CSF had no influence on that of the megakaryoblastic leukemic cells L-8057 and failed to prolong the median survival period of L-8057 leukemic mice. Receptor binding analysis revealed that L-8801 cells expressed a G-CSF receptor (Kd=125 pM, 479 binding sites/cell) and L-8057 cells had no G-CSF receptors. Then, we examined the growth potential of these cells. The median survival period was longer for mice implanted with L-8801 cells cultured with rhG-CSF for 72 h in vitro than for cells grown without rhG-CSF. Furthermore, the median survival period of mice implanted with spleen cells from L-8801 leukemic mice treated with rhG-CSF was prolonged compared with those from leukemic mice without rhG-CSF. In contrast, there was no effect of rhG-CSF on the growth potential of the spleen from L-8057 leukemic mice. The results of our present study demonstrate that rhG-CSF reduced the growth of L-8801 leukemic cells in vitro and in vivo mediated through G-CSF receptors, thereby suppressing the development of leukemia.
我们研究了重组人粒细胞集落刺激因子（rhG-CSF）对两种小鼠白血病细胞系增殖的体内外作用。rhG-CSF在甲基纤维素培养中刺激早幼粒细胞白血病细胞系L-8801形成白血病集落，并增加液体培养中L-8801细胞的数量。然而，rhG-CSF治疗延长了植入L-8801细胞的小鼠的中位生存期，并延迟了外周血中白血病原始细胞的出现。同时，rhG-CSF对巨核细胞白血病细胞L-8057没有影响，也未能延长L-8057白血病小鼠的中位生存期。受体结合分析显示，L-8801细胞表达G-CSF受体（Kd = 125 pM，479个结合位点/细胞），而L-8057细胞没有G-CSF受体。然后，我们检测了这些细胞的生长潜能。体外经rhG-CSF培养72小时的L-8801细胞植入的小鼠，其中位生存期比未用rhG-CSF培养的细胞植入的小鼠更长。此外，与未用rhG-CSF治疗的白血病小鼠相比，用rhG-CSF治疗的L-8801白血病小鼠的脾细胞植入的小鼠中位生存期延长。相反，rhG-CSF对L-8057白血病小鼠脾脏的生长潜能没有影响。我们目前的研究结果表明，rhG-CSF在体外和体内通过G-CSF受体介导降低L-8801白血病细胞的生长，从而抑制白血病的发展。
