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 grow th of hepatic metastasis of the tissue polypeptide antigen (TPA)-produ cing human colon cancer COL-1 was examined in severe combined immunode ficient (SCID) mice. Prior to this chemotherapeutic study, we confirme d 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 th e chemotherapy of experimental hepatic metastasis induced by intrasple nic injection of COL-1 cells, KRN5500 at 12 mg/kg per day was administ ered i.v. three times at 4-day intervals. From the start of chemothera py (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 r ange for intact SCID mice (409-634 U/l). The mean tumor weight was 4.8 7 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 tumo r growth inhibition rate of 85%. These results suggest the usefulness of TPA as a tumor marker in an experimental xenograft model. The chemo therapeutic efficacy of KRN5500 against experimental hepatic metastasi s indicates that it may be a useful drug for the treatment of patients with hepatic metastases of colon cancer.