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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
韦 丹,张 菡,尹富强,刘 夏
530021 南宁,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(韦 丹,张 菡,刘 夏),生命科学研究院(尹富强),区域性高发肿瘤早期防治研究教育部重点实验室(尹富强),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(刘 夏)
摘要:
[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3 β(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(IC50)=(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。
关键词:  Garcinone E  鼻咽癌  转移  细胞周期  自噬
DOI:10.3969/j.issn.1674-3806.2023.04.08
分类号:R 739.6
基金项目: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)
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
WEI Dan, ZHANG Han, YIN Fu-qiang, et al.
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
Abstract:
[Abstract] 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(IC50)=(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.
Key words:  Garcinone E  Nasopharyngeal carcinoma  Metastasis  Cell cycle  Autophagy