Inhibitory effect of a spicamycin derivative, KRN5500, on the growth of hepatic metastasis of human colon cancer-producing tissue polypeptide antigen

The inhibitory effect of KRN5500, a spicamycin derivative, on the growth of hepatic metastasis of the tissue polypeptide antigen (TPA)-producing human colon cancer COL-1 was examined in severe combined immunodeficient (SCID) mice. Prior to this chemotherapeutic study, we confirmed the high correlation coefficient (r = 0.86, P < 0.01) between plasma TPA levels in athymic nude;mice bearing COL-1 and tumor volume. In the chemotherapy of experimental hepatic metastasis induced by intrasplenic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administered i.v. three times at 4-day intervals. From the start of chemotherapy (day I), plasma TPA levels in the mice were significantly decreased from 8332 U/l to a minimum of 494 U/l on day 16 and were within the range for intact SCID mice (409-634 U/l). The mean tumor weight was 4.87 g in the liver of untreated mice on day 19 and 0.74 g, in the liver of KRN5500-treated mice, a significant difference, representing a tumor growth inhibition rate of 85%. These results suggest the usefulness of TPA as a tumor marker in an experimental xenograft model. The chemotherapeutic efficacy of KRN5500 against experimental hepatic metastasis indicates that it may be a useful drug for the treatment of patients with hepatic metastases of colon cancer.