Objective: This experiment was designed to study the effect of small molecule tripeptide CMS024 on tumor growth and metastasis in a nude mice model of human hepatocellular carcinoma (HCC) metastasis.
Methods: Highly metastatic human HCC cell strain HCCLM6 was injected into subcutaneous region of nude mice. When the subcutaneous tumor reached 0.8 cm in diameter, the tumor was removed and cut into small pieces about 1 mm in diameter and implanted orthotopically into the liver of 20 BALB/c nude mice, which were randomized into treatment group and control group each with 10 mice. The treatment group received daily CMS024 intraperitoneal injection at the dose of 300 microg/kg beginning from the second postoperative day. The control group 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 metastases were 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 g +/- 0.5 g in the treatment group and 2.3 g +/- 0.8 g in the control group (P > 0.05). The abdominal wall metastases and intraperitoneal metastases 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 metastases 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 metastases 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 tripeptide CMS024 demonstrated positive effects to retard tumor growth and inhibit loco-regional and long distance metastases in a nude mice model of human HCC metastasis, and no obvious toxic or side effects on the tumor bearing nude mice.