Abstract
OBJECTIVE:To examine the influence of Saponin Ⅰ from Shuiti anqi(Rhizoma Schizocapasae Plantagineae)(SSPH Ⅰ)on hepatocellular carcinoma(HCC)metastasis,and to elucidate the underlying mechanism.METHODS:The intrahepatic metastasis Bagg's Albino/c(BALB/c)mouse model was established with human hepatocellular carcinomas(HepG2)cells,then treated with normal saline(once per day),cisplatin(2 mg/kg,once every 2 d),and SSPH Ⅰ(25,50,and 75 mg/kg,once per day).Then,we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques.RESULTS:Based on our analysis,SSPH Ⅰ significantly alleviated hepatocyte necrosis and tumor cells infiltration.Moreover,SSPH Ⅰ suppressed extracellular matrix(ECM)degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2),MMP-9,CD31,CD34,and vascular endothelial growth factor(VEGF)levels.Furthermore,SSPH Ⅰ repressed invasion and meta-stasis by suppressing the transforming growth factor-β 1(TGF-β 1)/Smad7 axis and epithelial-mesenchymal transition(EMT),as evidenced by the scarce TGF-β1,N-cadherin,and Vimentin expressions,and elevated Smad7 and E-cadherin expressions.CONCLUSION:The SSPH Ⅰ-mediated negative regulation of the TGF-β 1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.
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