Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells.
OBJECTIVE
To assess the effect of Celastrus orbiculatus (COE) on growth, invasion and migration of human gastric cancer MGC-803 cells and to explore the possible mechanism.


METHODS
The effect of COE on cell viability, apoptosis, adhesion, invasion and migration were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometric, cell adhesion and transwell assay, respectively. The activity and expression of matrix metalloproteinase-9 (MMP-9) were determined by gelatin zymography, Western blot and quantitative real-time polymerase chain reaction analysis. Meanwhile, effects of COE on the expression of mitogen-activated protein kinases (MAPKs), serine threonine kinase (Akt), nuclear factor κB (NF-κB) were investigated with Western blot analysis.


RESULTS
COE inhibited proliferation and induced apoptosis of MGC-803 cells in a dose-dependent manner. When treated with low-toxic (below 80 μg/mL) doses of COE, cell adhesion, invasion and migration were markedly suppressed. Furthermore, the gelatinolytic activity and expression of MMP-9 were also remarkably suppressed in a dose-dependent manner. In addition, upstream signaling pathways, including the phosphatidylinositol-3 kinase (PI3K)/Akt and NF-κB, were suppressed by COE. Additionally, the PI3K/Akt inhibitor, LY294002, in treating MGC-803 cells potently suppressed cell invasion and migration as well as expression of MMP-9. Similarly, the combined treatment with COE and LY294002 showed a synergistic effect compared with the treatment with COE or LY294002 alone in MGC-803 cells.


CONCLUSIONS
COE inhibits invasion and migration of MGC-803 cells by reducing MMP-9 expression. It also inhibit PI3K/Akt and NF-κB signaling pathways, which may offer a novel approach for the treatment of human gastric cancer.
Institute of Traditional Chinese Medicine and Western Medicine, School of Medicine, Yangzhou University, Yangzhou, Jiangsu Province, 225009, China.
Yao-Dong
YD
Zhu
Yan-Qing
YQ
Liu
Ya-Yun
YY
Qian
Hua
H
Zhang
Guo-Qing
GQ
Li
Lin
L
Yang