M. Kamishohara et al., INHIBITORY EFFECT OF A SPICAMYCIN DERIVATIVE, KRN5500, ON THE GROWTH OF HEPATIC METASTASIS OF HUMAN COLON CANCER-PRODUCING TISSUE POLYPEPTIDE ANTIGEN, Cancer chemotherapy and pharmacology, 38(6), 1996, pp. 495-498
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.