南蛇藤提取物通过调控基质金属蛋白酶组及其抑制因子抑制人胃癌SGC-7901细胞侵袭转移的研究 Research on effect of <i>Celastrus</i><i> orbiculatus</i> extract on inhibiting invasion and metastasis of human gastric cancer SGC-7901 cells by mediating matrix metalloproteinases group and their inhibitors期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

南蛇藤提取物通过调控基质金属蛋白酶组及其抑制因子抑制人胃癌SGC-7901细胞侵袭转移的研究

引用本文：	王海波,顾昊,赵雪煜,冯俊,钱亚云,杨林,金凤,史有阳,陆松花,刘延庆. 南蛇藤提取物通过调控基质金属蛋白酶组及其抑制因子抑制人胃癌SGC-7901细胞侵袭转移的研究[J]. 中草药, 2016, 47(8): 1345-1350

作者姓名：	王海波顾昊赵雪煜冯俊钱亚云杨林金凤史有阳陆松花刘延庆

作者单位：	国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001;国家中医药管理局胃癌毒邪论治重点研究室, 江苏扬州 225001;扬州大学-扬州市肿瘤研究所, 江苏扬州 225001;扬州大学肿瘤防治重点实验室, 江苏扬州 225001;扬州大学医药研究所, 江苏扬州 225001

基金项目：	国家自然科学基金资助项目(81274141,81450051,81403232,81573656);江苏省自然科学基金(BK20141280);江苏省中医药科技项目(LZ11210)

摘要：	目的探讨南蛇藤提取物(COE)对人胃癌SGC-7901细胞的侵袭和转移的影响及其分子机制。方法 MTT法检测COE对人胃癌SGC-7901细胞增殖的影响;Transwell小室实验检测COE对SGC-7901细胞侵袭和转移能力的影响。Western blotting检测经COE作用后的SGC-7901细胞中金属基质蛋白酶(MMPs)MMP2、MMP9和金属基质蛋白酶抑制因子(TIMPs)TIMP1、TIMP3的蛋白水平。RT-PCR检测经COE作用后的SGC-7901细胞中MMP2、MMP9、TIMP1、TIMP3的m RNA表达情况。结果 Transwell实验显示,经20、40、80 mg/L COE处理过的SGC-7901细胞穿膜数明显减少并呈一定的浓度依赖性。Western blotting结果显示,经20、40、80 mg/L COE处理过的SGC-7901细胞,MMP2、MMP9蛋白的表达水平明显降低,而TIMP1、TIMP3蛋白表达水平明显上调。RT-PCR结果显示,经20、40、80 mg/L COE处理过的SGC-7901细胞中MMP2和MMP9的m RNA水平有轻微升高趋势,而TIMP1和TIMP3的m RNA水平明显大幅上调(P0.001)。结论 COE能明显抑制人胃癌SGC-7901细胞的侵袭和迁移,其机制可能与下调MMP2、MMP9蛋白水平直接相关。而其作用的实现,很可能是通过直接上调TIMP1和TIMP3的m RNA转录水平从而提高TIMPs蛋白表达水平实现的。
关键词：	南蛇藤胃癌金属基质蛋白酶金属基质蛋白酶抑制因子侵袭迁移
收稿时间：	2015-10-26
*Research on effect of Celastrus* orbiculatus extract on inhibiting invasion and metastasis of human gastric cancer SGC-7901 cells by mediating matrix metalloproteinases group and their inhibitors**

WANG Hai-bo,GU Hao,ZHAO Xue-yu,FENG Jun,QIAN Ya-yun,YANG Lin,JIN Feng,SHI You-yang,LU Song-hua and LIU Yan-qing. Research on effect of Celastrus orbiculatus extract on inhibiting invasion and metastasis of human gastric cancer SGC-7901 cells by mediating matrix metalloproteinases group and their inhibitors[J]. Chinese Traditional and Herbal Drugs, 2016, 47(8): 1345-1350

Authors:	WANG Hai-bo GU Hao ZHAO Xue-yu FENG Jun QIAN Ya-yun YANG Lin JIN Feng SHI You-yang LU Song-hua LIU Yan-qing

Affiliation:	The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of The State Administration of Traditional Chinese Medicine, Yangzhou 225001, China;Yangzhou Cancer Research Institute, Yangzhou University, Yangzhou 225001, China;The Key Laboratory of Cancer Prevention and Treatment, Yangzhou University, Yangzhou 225001, China;Medical & Pharmaceutical Institute of Yangzhou University, Yangzhou 225001, China

Abstract:	Objective To study the effect and the mechanism of Celastrus orbiculatus extract (COE) on inhibiting the invasion and metastasis of human gastric cancer SGC-7901 cells. Methods The groups of different cells were set up, such as negative control group, COE with different concentration groups, and positive control group. The effects of COE on the cytotoxicity and proliferation of human gastric cancer SGC-7901 cells were determined by MTT assay. The effect of COE on the metastatic ability of human gastric cancer SGC-7901 cells in vitro was observed by invasion assay and migration assay. The effects of COE on the expression of matrix metalloproteinases (MMPs) and their inhibitors in human gastric cancer SGC-7901 cells were examined by Western blotting. After the treatment in different groups, mRNAs of MMP2, MMP9, tissue inhibitors of metalloproteinases (TIMPs), TIMP1, and TIMP3 in cells were detected by RT-PCR. Results Compared with the negative control group, human gastric cancer SGC-7901 cells treated with COE at different concentration exhibited a dose-dependent growth inhibition. COE obviously reduced the migration and invasion potential of human gastric cancer SGC-7901 cells. In addition, the expression levels of MMP2 and MMP9 were dramatically suppressed by COE in a concentration-dependent manner, while the expression levels of TIMP1 and TIMP3 were raised. RT-PCR showed that mRNAs of TIMP1 and TIMP3 were raised with the increase of drug concentration. Conclusion COE could significantly inhibit the invasion and metastasis of human gastric cancer SGC-7901 cells via an up-regulation of the expression levels of TIMP1 and TIMP3 and down-regulation of the expression levels of MMP-2 and MMP-9.

Keywords:	Celastrus orbiculatus Thunb. human gastric cancer matrix metalloproteinases tissue inhibitors of metalloproteinases invasion metastasis
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