Hirofumi
Maruyama Tetsuro
Ikekawa ABSTRACT The present study demonstrates the antitumor effect of treatment combining protein-bound polysaccharide EA6 isolated from culinarymedicinal mushroom Flammulina velutipes with surgical excision (SE) in mice using Meth-A fibrosarcoma. Oral administration of EA6 alone exhibited no inhibitory effect on the growth of intradermally inoculated Meth-A tumor cells, although it was effective for increasing the lifespan in mice bearing Lewis lung carcinoma or B-16 melanoma. In Meth-A fibrosarcoma, EA6, when administered orally, displayed a marked antitumor effect against the same tumor rechallenged after SE. When oral administration of EA6 (10 mg/kg/day) was begun on post-excision day 1, the growth of the secondary tumor inoculated on post excision day 7 was significantly inhibited. When mice showed this inhibitory effect for the second solid tumor challenged, immune activity of the mice was tested. EA6 was found to enhance both humoral (i.e., antibody response to sheep red blood cells) and cell-mediated (i.e., anti-Meth-A delayed-type hypersensitivity response) immunity. In tumor neutralization tests, the spleen cells from mice treated with both EA6 and SE markedly inhibited the growth of admixed Meth-A tumor cells. The antitumor immunity of the spleen cells was eliminated by treatment with anti-CD4 monoclonal antibody plus complement, but not with anti-CD8 monoclonal antibody plus complement. These results suggest that EA6 augments the antitumor immunity in combination with SE, and the effect is mediated by CD4-positive T cells.
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