要約

The present study evaluated the antitumor activity of polyethylene glycol (PEG)-concentrated double-stranded RNA mycovirus, present abundantly in fresh 2-day-old buds of Lentinus edodes (shiitake mushroom). K36 cell-line induced murine lymphoma in male AKR mice was the tumor-model used. The difference in antitumor activity by three types of intervention in relation to leukemia cell inoculation was assessed. The three interventions were: prefeeding with mycovirus extract before K36 cell inoculation, simultaneously feeding of extract with K36 cell inoculation and administering the extract after tumors were induced. Tumors obtained 14 d after leukemia cell inoculation were investigated in detail. Prefeeding with mycovirus extract conferred the best antitumor activity with a tumor inhibition rate of 80.7% (p < 0.001). Simultaneous feeding and administering extract after tumors were induced were also effective with tumor regression rates of 73.8% (p < 0.001) and 67.6% (p < 0.001), respectively. In addition, the effective dose of mycovirus extract caused only a negligible body-weight reduction of 0.63% (p = 0.866) without any toxic effects in mice. Electron microscopy revealed apoptotic cells in all three regimens. These findings were confirmed by confocal microscopy on TUNEL-stained lymphoma sections, a hallmark of apoptosis. Interestingly, electron microscopy also revealed abundant defective tumor retrovirus in the prefed regimen and lesser in the other two regimens. Cytokines interferon-γ and tumor necrosis factor-α in serum from healthy mice was assayed after oral administration of the extract. These surrogate markers of immunomodulation were significantly elevated (p = 0.004 and p = 0.025, respectively). This proved the formulated hypothesis that immunomodulation by mycovirus extract contributed to the observed antitumor activity and production of defective tumor retrovirus.