Mori H, Saiki I, Koda A
Nihon Yakurigaku Zasshi. 1978 Nov;74(8):907-23. doi: 10.1254/fpj.74.907.
E.L.4 lymphosarcoma (E.L.4) s.c. as a syngeneic tumor was transplanted into C57BL/6 mice, 4 weeks old. The tumor growth was more rapid in male mice. An i.p. injection of alpha-MPG or DPA caused a decrease of the tumor growth and prolongation of the survival time in male mice. In contrast, an acceleration of the growth and a reduction of the survival time were observed in females dosed with alpha-MPG or DPA. Such a sexual difference and the activity of drugs decreased with the progress of age. alpha-MPG and DPA had little effect on the number of recovered and living E.L.4 cells in vitro. However, with the inoculation of alpha-MPG-treated E.L.4 into mice, the tumor rapidly grew in a dose dependent manner. On the other hand, there was a tendency toward suppression of the tumor growth when DPA was given. Development and growth of tumor in mice induced by 20-methylcholanthrene showed a tendency toward suppression in male mice when alpha-MPG in a dose of 5 mg/kg was given every other day, and in both sexes with the same dose of DPA. Responses of spleen and lymph node cells to phytohemagglutinin-P (PHA) or lipopolysaccharide (LPS) were reduced by the transplantation of E.L.4 in 4 week old mice. With alpha-MPG and DPA a reduction in PHA response of both the cells tended to recover, and that in LPS response of lymph node cells was recovered. In these mice, the decrease in cytotoxicity of spleen and lymph node cells against E.L.4 was recovered by treatment with both drugs. There was also a complement-dependent cytotoxicity against E.L.4 in their sera, and the activity was further increased by the administration of alpha-MPG. These findings suggest that alpha-MPG and DPA are anti-tumor agents which act through immune mechanisms.
将同基因肿瘤E.L.4皮下移植到4周龄的C57BL/6小鼠体内。肿瘤在雄性小鼠中生长更快。腹腔注射α - MPG或DPA可使雄性小鼠的肿瘤生长减缓,存活时间延长。相反,给雌性小鼠注射α - MPG或DPA后,观察到肿瘤生长加速,存活时间缩短。这种性别差异和药物活性随年龄增长而降低。α - MPG和DPA对体外回收的活E.L.4细胞数量影响不大。然而,将经α - MPG处理的E.L.4接种到小鼠体内后,肿瘤呈剂量依赖性快速生长。另一方面,给予DPA时,肿瘤生长有被抑制的趋势。当每隔一天给予5mg/kg剂量的α - MPG时,20 - 甲基胆蒽诱导的小鼠肿瘤在雄性小鼠中的发生和生长有被抑制的趋势,而相同剂量的DPA对两性均有抑制作用。4周龄小鼠移植E.L.4后,脾细胞和淋巴结细胞对植物血凝素 - P(PHA)或脂多糖(LPS)的反应降低。使用α - MPG和DPA后,两种细胞对PHA的反应降低趋势趋于恢复,淋巴结细胞对LPS的反应也得到恢复。在这些小鼠中,两种药物的处理可使脾细胞和淋巴结细胞对E.L.4的细胞毒性降低得到恢复。它们的血清中也存在针对E.L.4的补体依赖性细胞毒性,并且给予α - MPG后活性进一步增强。这些发现表明,α - MPG和DPA是通过免疫机制发挥作用的抗肿瘤药物。