SchizophyllanとNK-421の抗腫瘍,延命効果と細胞性免疫能増強効果

Antitumor activities and effects on cellular immunity of Schizophyllan (SPG), a highly purified polysaccharide extracted from the culture filtrate of Schizophyllum commune Fries, and Bestatin (NK-421), an inhibitor of aminopeptidase B discovered in the culture broth of Streptomyces olivoreticuli, were investigated. The optimal dose of SPG monotherapy to manifest an antitumor effect on MH-134 hepatomas transplanted into C3H/He mice was 10mg/kg, both intraperitoneally (i.p.) and subcutaneously (S.C.). The optimal timing of SPG monotherapy was observed in the group which was treated from 1 day after tumor transplantation, resulting in the most prolonged mean survival (MS) and the highest survival rate. In combined therapy with SPG and mitomycin C (MMC), the most prolonged MS was observed in the group which was treated with MMC on day 3 after tumor transplantation and combined with SPG from day 5. Moreover, the effectiveness continued when the same combined therapy was conducted after the removal of transplanted tumors. The highest ADCC activity by spleen cells harvested from the mice in the SPG monotherapy group was obtained on day 12 after tumor transplantation. The ADCC activity tended to become lower in the MMC monotherapy group, but in the combined therapy group with optimal timing, the highest ADCC activity mediated by non-adherent cells was observed on day 14 after tumor transplantation. Suppressed NK cell activity in tumor-bearing mice was increased to normal levels by SPG monotherapy. On the other hand, NK 421 monotherapy did not manifest a satisfactory antitumor effect regarding survival rate, although it potentiated ADCC activity over a wide range of doses, particularly 5 and 10mg/kg. The main cellular component exhibiting ADCC activity induced by NK 421 therapy seemed to be non-T-cells. By NK-421 monotherapy, the suppressed NK cell activity in tumor-bearing mice was restored up to the normal level.