Effects of Celastrus Orbiculatus Extracts On the Invasion and Metastasis Via Targeting Integrin Β4 in Gastric Cancer Cells
Zixin Yin1,2,3, Wei Qin1,2,3, Zewen Chu1,2,3, Tengyang Ni1,2,3, Yanqing Liu1,2,3 and Yayun Qian1,2,3*
1Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, China
2The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, China
3Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, China
Background： Gastric cancer is a malignant tumor that originates from the gastric mucosal epithelium and is formed by continuous cloning and proliferation of gastric epithelial cells and progenitor cells. Celastrus orbiculatus extract (COE) has been shown to inhibit the activity of many types of tumors.
Objective: The study aims to investigate the effects and the mechanisms of COE inhibiting the invasion and migration by targeting integrin β4 (ITGB4) in AGS and MKN45 cells.
Methods: COE was diluted to different concentrations (100, 200 and 400 μg/mL), and the cell proliferation was detected using the MTT assay. The effects of COE on the invasion and migration in the gastric cancer cells were evaluated by Transwell and wound healing assays. The invasion and migration of cells were further observed with a living cell motion tracking system. The expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transformation (EMT)-related proteins was detected by Western Blotting after COE treament for 24 h in the gastric cancer cells.
Results: COE obviously inhibited the proliferation of AGS and MKN45 cells. After COE treatment, the expression levels of MMP-2 and MMP-9 protein decreased, while the expression level of TIMP-1 increased. The expression level of N-cadherin and Vimentin decreased, while the expression level of E-cadherin increased. The protein expression levels of ITGB4, Akt, PI3K and Palladin were decreased.
Conclusion: COE inhibited the invasion and migration of AGS and MKN45 cells. which may be associated with the inhibition of ITGB4/PI3K/Akt/Palladin signaling pathway.
Celastrus orbiculatus extract; invasion; migration; human gastric cancer; ITGB4