Effects of thalidomide on angiogenesis and tumor growth and metastasis of human hepatocellular carcinoma in nude mice.
OBJECTIVE
To investigate the effects of thalidomide on angiogenesis, tumor growth and metastasis of hepatocellular carcinoma in nude mice.


METHODS
Twenty-four nude mice were randomly divided into therapy group and control group, 12 mice in each group. Thalidomide dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension was administered intraperitoneally once a day at the dose of 200 mg/kg in therapy group, and an equivalent volume of 0.5% CMC in control group. Mice were sacrificed on the 30th d, tumor size and weight and metastases in liver and lungs were measured. CD34 and VEGF mRNA in tumor tissue were detected by immunohistochemistry and semi-quantitative RT-PCR respectively and microvessel density (MVD) was counted. Serum concentrations of TNF-alpha and ALT and AFP were also tested.


RESULTS
MVD and VEGF mRNA in therapy group were less than those in control group (31.08+/-16.23 vessels/HP vs 80.00+/-26.27 vessels/HP, 0.0538+/-0.0165 vs 0.7373+/-0.1297, respectively, P<0.05). No statistical difference was observed in tumor size and weight and metastases in liver and lungs. TNF-alpha was significantly lower in therapy group than in control group (28.64+/-4.64 ng/L vs 42.69+/-6.99 ng/L, P<0.05). No statistical difference in ALT and AFP was observed between groups.


CONCLUSIONS
Thalidomide can significantly inhibit angiogenesis and metastasis of hepatocellular carcinoma. It also has inhibitory effects on circulating TNF-alpha.
Zhang
Zhong-Lin
ZL
Department of General Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China. zhangzhonglin221@sina.com
Liu
Zhi-Su
ZS
Sun
Quan
Q
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000473:pathology*; D002455:Cell Division; D017931:DNA Primers; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D013792:Thalidomide / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D020533:Angiogenesis Inhibitors; D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide