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| Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells |
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| KeyWord:Celastrus Orbiculatus, hepatocellular carcinoma, antimetastasis, epithelial-mesenchymal transition, Hif-1α /Twist1 signaling pathway |
| Author Name | Affiliation | E-mail | | QIAN Ya-yun | 1. Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province (225009), China
2. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu Province (225001), China
3. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province (225009), China | yyqian@yzu.edu.cn | | SHI You-yang, LU Song-hua, YANG Ting | | |
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| Abstract: |
| Objective: To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms. Methods: The effect of COE (160, 200 and 240 μ g/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl2 was used to establish a hypoxia model in vitro. Effects of COE on the expressions of E-cadherin, vimentin and N-cadherin were investigated with Western blot and immunofluorescence analysis, respectively. Results: COE inhibited proliferation and metastasis of hypoxia-induced hepatocellular carcinoma cells in a dose-dependent manner (P<0.01). Furthermore, the expression of epithelial-mesenchymal transition (EMT) related markers were also remarkably suppressed in a dose-dependent manner (P<0.01). In addition, the upstream signaling pathways, including the hypoxia-inducible factor 1α (Hif-1α ) and Twist1 were suppressed by COE. Additionally, the Hif-1α inhibitor 3-5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), potently suppressed cell invasion and migration as well as expression of EMT in hypoxia-induced HepG2 cells. Similarly, the combined treatment with COE and YC-1 showed a synergistic effect (P<0.01) compared with the treatment with COE or YC-1 alone in hypoxia-induced HepG2 cells. Conclusions: COE significantly inhibited the tumor metastasis and EMT by suppressing Hif-1α /Twist1 signaling pathway in hypoxia-induced HepG2 cell. Thus, COE might have potential effect to inhibit the progression of HepG2 in the context of tumor hypoxia. |
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