Cinobufacini inhibits epithelial-mesenchymal transition of human hepatocellular carcinoma cells through c-Met/ERK signaling pathway
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- Qi Fanghua
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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- Wang Jinjing
- Shandong University of Traditional Chinese Medicine
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- Zhao Lin
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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- Cai Pingping
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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- Tang Wei
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo
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- Wang Zhixue
- Department of Traditional Chinese Medicine, Shandong Provincial Hospital affiliated to Shandong University
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<p>Cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad Bufo bufo gargarizans Cantor, is a well known traditional Chinese medicine widely used in clinical cancer therapy in China. Its therapeutic effect is especially pronounced in liver cancer. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. Here, we investigated the effects and mechanisms of cinobufacini on inhibiting HepG2 cells invasion and metastasis. Epithelial-mesenchymal transition (EMT) is identified as an important initiation step for HCC metastasis. After the HepG2 cells were treated with different concentrations of cinobufacini, the expression of EMT related E-cadherin was increased while N-cadherin and Vimentin were decreased, and the expression of EMT related transcription factors Snail and Twist were decreased. Moreover, the phosphorylation of c-Met was inhibited by cinobufacini, and the expression of MEK1/2 and ERK1/2, the downstream kinase of the signal transduction pathway activated by c-Met, also decreased in a dose-dependent manner with cinobufacini. In addition, after the cells were treated with different concentrations of cinobufacini, there was a significant decrease in MMP-2 and MMP-9 expression in HepG2 cells. In conclusion, the current study suggested cinobufacini could prevent HepG2 cells migration and invasion via inhibiting EMT through c-Met/ERK signaling pathway, which might provide experimental evidence for cinobufacini treatment of HCC.</p>
収録刊行物
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- BioScience Trends
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BioScience Trends 12 (3), 291-297, 2018-06-30
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会
