Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice

Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice
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DOI:
10.1023/a:1008054111445
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发表时间:
1998-01-01
期刊:
BIOTHERAPY
影响因子:
--
通讯作者:
Fujimiya, Y
Fujimiya, Y
中科院分区:
其他
文献类型:
--
作者:
Ebina, T;Fujimiya, Y

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在双移植肿瘤系统中检测了从巴西蘑菇子实体获得的提取物的抗肿瘤效果,其中BALB/c小鼠同时接受右侧(10(6)个细胞)和左侧(2 × 10(5)个细胞)的Meth-A肿瘤细胞颗粒的皮内注射,然后注射5 mg巴西蘑菇提取物。在第3、4和5天在右侧肿瘤中注射Blazei。瘤内施用乙醇可溶性(级分I)、水-乙醇可溶性(级分2)、碳酸铵可溶性(级分3)和碳酸铵不溶性(级分4)级分导致肿瘤生长的抑制,其中级分3显示出最大的杀肿瘤活性,产生右侧肿瘤的消退和左侧非注射肿瘤的生长抑制。使用0.5mg级分3获得最大效果,并将该量用于随后的实验。肿瘤内给药的级分3的抗肿瘤作用通过口服任意给药含有0.083%级分3的饲料而增强。将肿瘤内给予0.5 mg级分3治愈的小鼠的免疫脾细胞直接注射(2 × 10(7)个细胞/小鼠)到Meth-A肿瘤中时,肿瘤生长受到抑制。将第7天来自级分3处理的右侧肿瘤和左侧肿瘤的肿瘤细胞培养24小时,并测定其培养上清液的嗜中性粒细胞或巨噬细胞趋化活性。在左侧肿瘤组织的培养基中检测到显著的巨噬细胞趋化因子活性。由活化的巨噬细胞和中性粒细胞产生的免疫抑制酸性蛋白(IAP)的血清水平在皮内注射0.5 mg级分3后不久短暂升高。这些结果表明,左侧未注射肿瘤的消退是由于免疫反应,涉及诱导脾细胞毒性细胞,并在远处肿瘤中释放趋化因子。
The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells grain both the right (10(6) cells) and left flank (2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction I), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibitition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 x 10(7) cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left noninjected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of chemotactic factors in the distant tumor.