ANTITUMOR-ACTIVITY OF (2''R)-4'-O-TETRAHYDROPYRANYL ADRIAMYCIN ON HUMAN GASTRIC-CANCER CELL-LINES IN-VITRO AND IN-VIVO

The antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin (pirarubicin; THP) was assessed using human gastric cancer cell lines in vitro and in vivo. The cytotoxicity of THP on MKN-28 and MKN-45 was superior to that of adriamycin (ADM) as detected by a growth assay with an MTT colorimetric endpoint. When the same doses of THP and ADM were administered intraperitoneally to nude mice bearing St-15, St-40 and SC-1-NU, the antitumor activity of THP was almost equivalent to ADM in terms of relative mean tumor weight. However, the adverse effects of THP were also significantly lower than those of ADM in terms of death rate, body weight loss and spleen weight loss. This was also confirmed in THP or ADM combination chemotherapy with mitomycin C and 5-fluorouracil on St-15 and MKN-45. These results indicated that THP is a candidate anthracycline to replace ADM for combination cancer chemotherapy in gastric carcinoma.