Study on the inhibitory effect of tyroserleutide on tumor growth and metastasis in nude mice model of human hepatocellular carcinoma metastasis.
OBJECTIVE
Previous study has shown that small tripeptide tyroserleutide has inhibitory effect on liver cancer both in vitro and in vivo. This study was designed to test the effect of tyroserleutide on tumor growth and metastasis in a nude mice model of human hepatocellular carcinoma (HCC) metastasis.


METHODS
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.
Li
Peng-Cheng
PC
Department of Oncology, Zhongnan Hospital of Wuhan University & Cancer Center of Wuhan University Wuhan, China.
Li
Yan
Y
Tang
Zhao-You
ZY
Wang
Lu
L
Lu
Rong
R
Xue
Qiong
Q
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary*; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000627:therapeutic use*
D009842:Oligopeptides; C484773:H-Tyr-Ser-Leu-OH