Abstract
BackgroundEchinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. However, the effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells.MethodsTwo types of liver cancer cells Huh7 and HepG2 were treated with different doses of ECH at different times and gradients. MTT and colony formation assays were used to determine the effects of ECH on the viability of Huh7 and HepG2 cells. Transwell assays and flow cytometry assays were used to detect the effects of ECH treatment on the invasion, migration, apoptosis and cell cycle of Huh7 and HepG2 cells. Western blot analysis was used to detect the effects of ECH on the expression levels of TGF-β1, smad3, smad7, apoptosis-related proteins (Caspase-3, Caspase-8), and Cyto C in liver cancer cells. The relationship between miR-503-3p and TGF-β1 was detected using bioinformatics analysis and Luciferase reporter assay.ResultsThe results showed that ECH inhibited the proliferation, invasion and migration of Huh7 and HepG2 cells in a dose- and time-dependent manner. Moreover, we found that ECH caused Huh7 and HepG2 cell apoptosis by blocking cells in S phase. Furthermore, the expression of miR-503-3p was found to be reduced in liver tumor tissues, but ECH treatment increased the expression of miR-503-3p in Huh7 and HepG2 cells. In addition, we found that TGF-β1 was identified as a potential target of miR-503-3p. ECH promoted the activation of the TGF-β1/Smad signaling pathway and increased the expression levels of Bax/Bcl-2. Moreover, ECH could trigger the release of mitochondrial Cyto C, and cause the reaction Caspases grade.ConclusionsThis study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer.
Highlights
Liver cancer is one of the most common malignant tumors with a high incidence rate, and the incidence of liver cancer has been growing rapidly [1]
This study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer
Effect of ECH on human liver cancer cell activity and proliferation To investigate the effect of ECH on human liver cancer cell function, MTT assay was performed and the results showed that the cell viability of HepG2 (Fig. 2a) and Huh7 (Fig. 2b) was gradually decreased with the increase of dose and time of ECH treatment compared with the control group (p < 0.01)
Summary
Liver cancer is one of the most common malignant tumors with a high incidence rate, and the incidence of liver cancer has been growing rapidly [1]. Cistanches Herba is rich in types of chemical components, and researchers at home and abroad have isolated more than a hundred compounds from it, including phenylethanol glycosides, lignans, cycloaliphatic terpenes, sugars, amino acids, etc. Echinacoside(ECH) is the main component of Cistanches Herba and is generally considered as its main active ingredient [6]. Studies have shown ECH may be a new treatment option for aggressive or widely metastatic tumors [8]. There is no report about the effect of ECH on the progression of liver cancer. Echinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. The effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells
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