Highly metastatic human HCC cell HCCLM6 was used to construct orthotopic implantation model of HCC
metastasis in 20 BALB/c-nu/nu nude mice, which were randomized into treatment group and control group each with 10 mice. The former received daily
CMS024 intraperitoneal injection at the dose of 300 microg/kg beginning from the second postoperative day, and the latter received
intraperitoneal injection of equal amount of 0.85%
sodium chloride solution. The mice were observed for signs of disease development. Thirty-five days later, the mice were sacrificed and abdominal and pulmonary
metastasis was recorded and peripheral blood hematological and biochemical parameters were determined.
RESULTS: After 35 days of intervention, all the 10 mice in the treatment group were alive and well, but there were only 9 living mice in the control group. The mean
tumor weights were 1.9 +/- 0.5 g in the treatment group and 2.3 +/- 0.8 g in the control group (P > 0.05). The abdominal wall
metastasis and intraperitoneal
metastasis were 100% for the control group and only 60% and 50%, respectively, for the treatment group (P < 0.05). Bloody
ascites and gross intrahepatic metastatic nodules were found in 70% and 90% of nude mice, respectively for the control group, and 20% and 40%, respectively, for the treatment group (P > 0.05). The median number of grades I, II, III and IV pulmonary
metastasis were 92, 24, 15 and 16, respectively, for the control group, and 24, 20, 10 and 8, respectively, for the treatment group. There were statistically significant differences in the number of grade I pulmonary
metastasis between the treatment group and the control group (24 vs. 92, P < 0.05). No statistically significant differences in the
body weight, peripheral blood hematological and biochemical parameters were observed between the two groups. No toxic effects were observed during the observation period.
CONCLUSIONS: Small molecule
tyroserleutide demonstrated positive effects to retard
tumor growth and inhibit loco-regional and long distance
metastasis in a nude mice model of human HCC
metastasis, and no obvious toxic or side effects on the
tumor bearing nude mice.