Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells
Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells
复制标题
DOI：
10.1007/s11655-014-1951-y
复制
发表时间：
2014-11
影响因子：
2.9
通讯作者：
Yao-dong Zhu;Yanqing Liu;Yayun Qian;Hua-Ping Zhang;Guoqing Li;Lin Yang
中科院分区：
文献类型：
--
作者：
Yao-dong Zhu;Yanqing Liu;Yayun Qian;Hua-Ping Zhang;Guoqing Li;Lin Yang
目的探讨南蛇藤（COE）对人胃癌MGC-803细胞生长、侵袭和迁移的影响，并探讨其可能的作用机制。方法采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）法、流式细胞术、细胞粘附法和Transwell实验分别研究COE对细胞活力、凋亡、粘附、侵袭和迁移的影响。通过明胶酶谱、Western blot 和实时定量聚合酶链式反应分析测定基质金属蛋白酶 9 (MMP-9) 的活性和表达。同时，通过Western blot分析COE对丝裂原激活蛋白激酶（MAPKs）、丝氨酸苏氨酸激酶（Akt）、核因子κB（NF-κB）表达的影响。结果COE以剂量依赖性方式抑制MGC-803细胞增殖并诱导细胞凋亡。当用低毒（低于 80 μg/mL）剂量的 COE 处理时，细胞粘附、侵袭和迁移均受到显着抑制。此外，MMP-9的明胶分解活性和表达也以剂量依赖性方式显着受到抑制。此外，上游信号通路，包括磷脂酰肌醇-3 激酶 (PI3K)/Akt 和 NF-κB，均被 COE 抑制。此外，PI3K/Akt 抑制剂 LY294002 在处理 MGC-803 细胞时可有效抑制细胞侵袭和迁移以及 MMP-9 的表达。同样，COE和LY294002联合处理与单独用COE或LY294002处理MGC-803细胞相比显示出协同作用。结论COE通过降低MMP-9表达来抑制MGC-803细胞的侵袭和迁移。它还抑制 PI3K/Akt 和 NF-κB 信号通路，这可能为人类胃癌的治疗提供新的方法。
ObjectiveTo assess the effect ofCelastrus orbiculatus(COE) on growth, invasion and migration of human gastric cancer MGC-803 cells and to explore the possible mechanism.MethodsThe 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.ResultsCOE 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.ConclusionsCOE 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.