Saponin Ⅰ from Shuitianqi () inhibits metastasis by negatively regulating the transforming growth factor-β1/Smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model

水天七皂苷Ⅰ通过负向调节转化生长因子-β1/Smad7 网络和上皮-间质转化抑制肝内转移 Bagg's Albino/c 小鼠模型中的转移

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作者:Lyu Meixian, Zhou Huan, Zhi Limin, Zhou Jinling, Gan Rizhi, Qin Yanping, H E Nengting, Zuo Qiqi, L I Hao, Dong Min, Liang Gang

Conclusion

The SSPH Ⅰ-mediated negative regulation of the TGF-β1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

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.

Objective

To examine the influence of Saponin I from Shuitianqi (Rhizoma Schizocapasae Plantagineae) (SSPH I) on hepatocellular carcinoma (HCC) metastasis, and to elucidate the underlying mechanism.

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 viaa 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-β1 (TGF-β1)/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.

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