Extracts of Celastrus Orbiculatus Inhibit Cancer Metastasis by Down-regulating Epithelial-Mesenchymal Transition in Hypoxia-Induced Human Hepatocellular Carcinoma Cells.
10.1007/s11655-018-2562-9
- Author:
Ya-Yun QIAN
1
;
You-Yang SHI
2
;
Song-Hua LU
2
;
Ting YANG
2
;
Xue-Yu ZHAO
2
;
Yan YAN
2
;
Wen-Yuan LI
2
;
Yan-Qing LIU
2
Author Information
1. Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China. yyqian@yzu.edu.cn.
2. Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China.
- Publication Type:Journal Article
- Keywords:
Celastrus Orbiculatus;
Hif-1 α/Twist1 signaling pathway;
antimetastasis;
epithelial-mesenchymal transition;
hepatocellular carcinoma
- MeSH:
Biomarkers, Tumor;
metabolism;
Carcinoma, Hepatocellular;
drug therapy;
pathology;
Celastrus;
chemistry;
Cell Hypoxia;
drug effects;
Cell Proliferation;
drug effects;
Cell Shape;
drug effects;
Cobalt;
Down-Regulation;
drug effects;
Epithelial-Mesenchymal Transition;
drug effects;
Hep G2 Cells;
Humans;
Liver Neoplasms;
drug therapy;
pathology;
Neoplasm Invasiveness;
Neoplasm Metastasis;
Neoplasm Proteins;
metabolism;
Plant Extracts;
pharmacology;
therapeutic use;
Signal Transduction;
drug effects
- From:
Chinese journal of integrative medicine
2019;25(5):334-341
- CountryChina
- Language:English
-
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. CoCl 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 1 α (Hif-1 α) and Twist1 were suppressed by COE. Additionally, the Hif-1 α 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-1 α/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.
