[Antitumor effect of a novel antitumor compound, NC-190, in the double grafted tumor system].
The antitumor effect of NC-190, N-beta-dimethylaminoethyl-9-carboxy-5-hydroxy-10-methoxybenzo [alpha] phenazine-6-carboxamide sodium salt, with a new experimental mouse model was studied. Intratumoral administration of NC-190 strongly inhibited the growth of Meth-A solid tumors in male BALB/c mice and led to a complete tumor regression and also resistance to the reinoculated tumor. Subsequently, the anti-metastatic effect of NC-190 was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 25 micrograms of NC-190 in the right tumor on days 3, 4 and 5. NC-190 inhibited the growth of not only the right but also the left, non-treated tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of NC-190. Adoptive transfer of NC-190 immunized spleen cells caused a complete regression of Meth-A tumors. The effector cell activity was lost only after treatment with anti-Lyt-2 antibody. These results suggest that intratumoral administration of NC-190 might induce Lyt-2 positive cytotoxic cells in the spleen and the left, non-treated tumor. In BALB/c nude mice, NC-190 inhibited slightly the growth of the right tumor but did not that of the left tumor. Therefore, the antitumor activity of NC-190 in the double grafted tumor system was judged as associated with a sequential immune mechanism in which T cells may play an important role. TILs (tumor infiltrating lymphocytes) obtained from the left and right sides tumors treated with NC-190 were examined by Winn assay for their antitumor activity against Meth-A sarcoma in BALB/c mice. TILs obtained from neither sides inhibited the growth of admixed Meth-A cells. Different from immunopotentiators such PSK or IL-1, NC-190 enhanced neither concomitant immunity nor sinecomitant immunity.
Ebina
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T
Dept. of Bacteriology, Tohoku University School of Medicine.
Shishido
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Murata
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K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods*; D010619:Phenazines / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000970:Antineoplastic Agents; D010619:Phenazines; C059048:NC 190