Kobayashi M, Nagayasu H, Hamada J, Takeichi N, Hosokawa M
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Exp Hematol. 1994 May;22(5):454-9.
We have examined the differentiation-inducing effects of ONO-4007, a new synthetic lipid A derivative with low endotoxic activities, on a rat myelomonocytic cell line, c-WRT-7, in vitro and in vivo. ONO-4007 induced the differentiation of c-WRT-7 cells into macrophage-like cells and inhibited the proliferation of c-WRT-7 cells in vitro. Stimulation with ONO-4007 induced messenger RNA expression of interleukin-1 alpha (IL-1 alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha), which have been reported to induce differentiation of several leukemia cell lines. However, autocrine production of these cytokines may not be involved in the mechanisms of differentiation induced by ONO-4007, because the treatment with IL-1 alpha, IL-6, or TNF-alpha does not induce the differentiation of c-WRT-7 cells. In vivo treatment by intravenous administration of ONO-4007 resulted in a significant prolongation of survival time of the rats inoculated intravenously with c-WRT-7 cells compared with that of untreated rats. These results suggest that ONO-4007 can be therapeutically useful for the treatment of leukemia.
我们已经在体外和体内研究了一种具有低内毒素活性的新型合成脂多糖衍生物ONO - 4007对大鼠骨髓单核细胞系c - WRT - 7的分化诱导作用。ONO - 4007在体外诱导c - WRT - 7细胞分化为巨噬细胞样细胞，并抑制c - WRT - 7细胞的增殖。用ONO - 4007刺激可诱导白细胞介素 - 1α（IL - 1α）、IL - 6和肿瘤坏死因子 - α（TNF - α）的信使核糖核酸表达，据报道这些因子可诱导几种白血病细胞系的分化。然而，这些细胞因子的自分泌产生可能不参与ONO - 4007诱导的分化机制，因为用IL - 1α、IL - 6或TNF - α处理并不会诱导c - WRT - 7细胞分化。与未处理的大鼠相比，通过静脉注射ONO - 4007进行体内治疗可显著延长静脉接种c - WRT - 7细胞的大鼠的存活时间。这些结果表明，ONO - 4007在白血病治疗中可能具有治疗作用。
