Journal of Traditional Chinese Medicine >
Saponin Ⅰ from Shuitianqi (Rhizoma Schizocapasae Plantagineae) 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
Received date: 2023-03-21
Accepted date: 2023-08-29
Online published: 2024-07-15
Supported by
National Natural Science Foundation of China, a New Anti-cancer Plant drug, Saponin Ⅰ from Shuitianqi (Rhizoma Schizocapasae Plantagineae), against Invasion and Metastasis of Non-small Cell Lung Cancer and Reversing Tyrosine Kinase Inhibitors Resistance basing on Human Growth Factor/c-Mesenchymal to Epithelial Transition Factor Pathway and its Molecular Mechanism of Regulating Epithelial-Mesenchymal Transition(8164062);Natural Science Foundation of Guangxi Province, Study on the Anti-hepatic Fibrosis Mechanism of Saponins from Shuitianqi (Rhizoma Schizocapasae Plantagineae) based on Transforming Growth Factor-β/Smad Signaling Pathway(2019GXNSFAA245075)
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.
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 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.
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.
Meixian LYU , Huan ZHOU , Limin ZHI , Jinling ZHOU , Rizhi GAN , Yanping QIN , Nengting HE , Qiqi ZUO , Hao LI , Min DONG , Gang LIANG . Saponin Ⅰ from Shuitianqi (Rhizoma Schizocapasae Plantagineae) 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[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 642 -651 . DOI: 10.19852/j.cnki.jtcm.2024.04.006
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