A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae
Autor: | Lei Song, Sha-Sha Bai, Qi Wang, Ming Hong, Yu Feng, Yi Luo, Gan-Qing He, Siying Li, Yujie Huang, Hong-Lian Shi, Mohammed M. Almutairi, Sha Li |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Hepatocellular carcinoma
Radix Salviae Miltiorrhizae medicine.disease_cause 01 natural sciences Flow cytometry 03 medical and health sciences 0302 clinical medicine In vivo medicine Protein kinase B PI3K/AKT/mTOR pathway Pharmacology medicine.diagnostic_test Cell growth Chemistry lcsh:Other systems of medicine Cell cycle lcsh:RZ201-999 digestive system diseases 030205 complementary & alternative medicine 0104 chemical sciences 010404 medicinal & biomolecular chemistry Complementary and alternative medicine Cancer research Signal transduction Carcinogenesis Network pharmacology |
Zdroj: | Chinese Medicine, Vol 14, Iss 1, Pp 1-17 (2019) |
ISSN: | 1749-8546 |
Popis: | Background Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Methods In this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC. Results In total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice. Conclusions We provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC. |
Databáze: | OpenAIRE |
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