山竹果皮提取物Garcinone E对鼻咽癌S18细胞迁移和侵袭的影响及相关机制研究  

A study on the effects of Garcinone E extracted from Mangostema mangostema peel on the migration and invasion of nasopharyngeal carcinoma S18 cells and their related mechanisms

作　　者：韦丹[1] 张菡 尹富强 刘夏[1,4] WEI Dan;ZHANG Han;YIN Fu-qiang(Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education,Center for Translational Medicine,Institute of Neuroscience and Guangxi Key Laboratory of Brain Science,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学转化医学研究中心“长寿与老年相关疾病”教育部重点实验室、神经科学研究所“广西脑科学研究”重点实验室,南宁530021 [2]广西医科大学生命科学研究院,南宁530021 [3]广西医科大学区域性高发肿瘤早期防治研究教育部重点实验室,南宁530021 [4]广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心、广西再生医学重点实验室,南宁530021

出　　处：《中国临床新医学》2023年第4期348-353,共6页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：国家自然科学基金地区基金项目(编号:82260721,81660606);国家自然科学基金青年基金项目(编号:81903644);广西自然科学基金面上项目(编号:2018GXNSFAA281227);2022年广西研究生教育创新计划项目(编号:YCSW2022215)。

摘　　要：目的探讨山竹果皮提取物Garcinone E对鼻咽癌S18细胞迁移和侵袭的影响及相关机制。方法使用不同浓度的Garcinone E处理S18细胞,通过CCK-8法检测细胞活力,通过Transwell实验检测S18细胞迁移、侵袭能力。通过Western blot实验检测S18细胞转移相关蛋白[组织金属蛋白酶抑制剂1(TIMP1)、组织金属蛋白酶抑制剂2(TIMP2)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)]、周期相关蛋白[细胞周期依赖性蛋白激酶抑制因子1A(p21)、周期蛋白依赖性激酶2(CDK2)、周期蛋白依赖性激酶6(CDK6)、周期蛋白依赖性激酶7(CDK7)、细胞周期蛋白B1(cyclin B1)]及自噬相关蛋白[微管相关蛋白1轻链3β(LC3B)、泛素结合蛋白p62(SQSTM1/p62)、苄氯素1(beclin-1)、自噬相关蛋白3(Atg3)]的表达水平。结果Garcinone E能够显著抑制S18细胞增殖(P<0.05),半抑制浓度(IC 50)=(3.34±0.03)μmol/L,并对S18细胞的迁移和侵袭能力均具有抑制作用(P<0.05)。Garcinone E可以上调S18细胞的TIMP1、TIMP2、p21、LC3B、SQSTM1/p62、beclin-1和Atg3蛋白的表达水平(P<0.05),下调MMP-2、MMP-9、CDK2、CDK6、CDK7和cyclin B1蛋白的表达水平(P<0.05)。结论Garcinone E能抑制鼻咽癌S18细胞的转移和侵袭能力,阻滞细胞周期,抑制细胞自噬,可作为鼻咽癌化疗药物研发的候选先导化合物。Objective To investigate the effects of Garcinone E extracted from Mangostema mangostema peel on the migration and invasion of nasopharyngeal carcinoma S18 cells and their related mechanisms.Methods Different concentrations of Garcinone E were used to treat S18 cells.The cell viability was detected by CCK-8 method,and the migration and invasion ability of S18 cells were detected by Transwell assay.Western blot was used to detect the expression levels of transfer-related proteins[tissue inhibitor of metalloproteinase 1(TIMP1),tissue inhibitor of metalloproteinase 2(TIMP2),matrix metallopeptidase 2(MMP-2),matrix metallopeptidase 9(MMP-9)],cyclin-related proteins[cyclin-dependent kinase inhibitor 1A(p21),cyclin-dependent kinase 2(CDK2),cyclin-dependent kinase 6(CDK6),cyclin-dependent kinase 7(CDK7),cyclin B1]and autophagy-related proteins[microtubule-associated protein 1 light chain 3 beta(LC3B),ubiquitin-binding protein p62(SQSTM1/p62),beclin-1,autophagy-related 3(Atg3)]in S18 cells.Results Garcinone E could significantly inhibit the proliferation of S18 cells(P<0.05),and its fifty percent inhibitory concentration(IC 50)=(3.34±0.03)μmol/L,and could inhibit the migration and invasion ability of S18 cells(P<0.05).Garcinone E could up-regulate the expression levels of TIMP1,TIMP2,p21,LC3B,SQSTM1/p62,beclin-1 and Atg3 proteins in S18 cells(P<0.05),and could down-regulate the expression levels of MMP-2,MMP-9,CDK2,CDK6,CDK7 and cyclin B1(P<0.05).Conclusion Garcinone E can inhibit the metastasis and invasion ability of nasopharyngeal carcinoma S18 cells,block cell cycle and inhibit autophagy,and can be used as a candidate lead compound for the development of chemotherapy drug for nasopharyngeal carcinoma.

关 键 词：Garcinone E 鼻咽癌 转移 细胞周期 自噬 

分 类 号：R739.6[医药卫生—肿瘤]