Tanshinone II-A inhibits invasion and metastasis of human hepatocellular carcinoma cells in vitro and in vivo.
OBJECTIVE
Tanshinone II-A is an alcohol extract of the root of the traditional Chinese medicinal plant Salvia miltiorrhiza Bunge, whose effects and mechanism in tumor metastasis are still unclear. The aim of this study was to investigate the effects of tanshinone II-A on tumor invasion and metastasis in human hepatocellular carcinoma (HCC) and its possible mechanism of action.


METHODS
The HCC cell lines HepG2 and SMMC-7721 were treated with tanshinone II-A at different doses. Invasion and metastasis of tumor cells were examined by in vitro and in vivo assays. The molecular mechanisms of tanshinone II-A for inhibiting invasion and metastasis of HCC cells were investigated by Western blot and gelatin zymography.


RESULTS
Treatment with tanshinone II-A had inhibitory effects on the migration and invasion of HCC cells. Increasing doses resulted in enhanced inhibitory effects. At 0.5 mg/L, the inhibitory effect was noticeable. At 1 mg/L, the inhibitory rate was 53.15%. The inhibitory effect became stronger with time; among 24, 48, 72 and 96 hours of treatment, the most significant effects were observed at 72 hours. Tanshinone II-A also significantly inhibited in vivo metastasis of HepG2 cells. Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of HCC cells by reducing the expression of the metalloproteinases MMP2 and MMP9 and by blocking NF-kappa B activation.


CONCLUSIONS
Tanshinone II-A effectively inhibited invasion and metastasis of HCC cells in vitro and in vivo, partly by inhibiting the activity of MMP2 and MMP9, and partly via the NF-kappa B signal transduction pathway.
Yuxian
Xu
X
Department of Epidemiology, Faculty of Preventive Medicine, Fourth Military Medical University, Xi'an, China.
Feng
Tian
T
Ren
Li
L
Zhengcai
Liu
L
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010616:Phenanthrenes / Q000494:pharmacology*; D027561:Salvia miltiorrhiza; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D010616:Phenanthrenes; C021751:tanshinone; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9