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| AKT抑制剂DC885对鼻咽癌细胞迁移侵袭能力的抑制及其机制 | |
| 引用本文： | 秦娟,邓蓉,戢娇,冯公侃,陈文丹,常少华,丁克,朱孝峰. AKT抑制剂DC885对鼻咽癌细胞迁移侵袭能力的抑制及其机制[J]. 陕西肿瘤医学, 2013, 0(11): 2393-2397 |
| 作者姓名： | 秦娟 邓蓉 戢娇 冯公侃 陈文丹 常少华 丁克 朱孝峰 |
| 作者单位： | [1]中山大学肿瘤防治中心华南肿瘤学国家重点实验室,广东广州510060 [2]川北医学院第二临床学院南充市中心医院肿瘤分院,四川南充637000 [3]中国科学院广州生物医药与健康研究院,广东广州510030 |
| 基金项目： | 国家重大科学研究计划课题（编号：2012CB967004）;国家自然科学基金青年基金项目（编号：81001446）;广东省自然科学基金面上项目（编号：S2012010008761）;中山大学青年教师培育项目（编号：Grant10ykpy39） |
| 摘 要： | 目的：探讨2-嘧啶-5-酰胺基噻唑类AKT抑制剂DC885对鼻咽癌细胞迁移侵袭能力的抑制及其机制.方法：AKT激酶活性实验检测DC885在体外对AKT激酶活性的影响；MTT法检测DC885对细胞增殖的影响；细胞划痕实验测定细胞迁移能力；Transwell小室实验测定细胞迁移力和侵袭力；蛋白质印迹检测细胞AKT及其下游底物磷酸化水平、MMP2、MMP9、EMT相关指标的表达.结果：DC885在体外抑制AKT激酶活性,并下调AKT下游底物的磷酸化水平.当使用较低浓度（1.25、2.5、5μmol/L）的DC885作用细胞24h,对鼻咽癌细胞增殖的影响并不显著.与对照组相比,实验组细胞的迁移和侵袭能力受到抑制,差异具有统计学意义（划痕实验（H=15.025,P＜0.01）、Transwell细胞迁移实验（H=14.608,P＜0.01）、Transwell细胞侵袭实验（H=14.980,P＜0.01）.不同浓度DC885抑制MMP2、MMP9的蛋白表达水平并呈浓度依赖性.DC885上调E-cadherin、α-Catenin表达水平,下调Vimentin、Fibronectin表达水平,均呈浓度依赖性.结论：DC885对鼻咽癌细胞迁移和侵袭能力有显著抑制作用,其机制可能与抑制MMP2、MMP9的表达水平、逆转EMT现象有关. |
| 关 键 词： | DC885 鼻咽癌 迁移 侵袭 |
2-pyrimidy-5-amidothiazole compounds AKT inhibitor DC885 represses the invasion and migration of human nasopharyngeal carcinoma cells and its mechanism |
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| Affiliation: | Qin Juan(State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yet-sen University, Guangdong Guangzhou 510060, China ; Cancer Center, Nanchong Central Hospital, the Second Clinical College of North Sichuan Medical College, Sichuan Nanchong 637000, China) Deng Rong(State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yet-sen University, Guangdong Guangzhou 510060, China) Ji Jiao(State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yet-sen University, Guangdong Guangzhou 510060, China) Feng Gongkan(State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yet-sen University, Guangdong Guangzhou 510060, China) Chen Wendan(State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yet-sen University, Guangdong Guangzhou 510060, China) Chang Shaohua(Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangdong Guangzhou 510030, China) Ding Ke(Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangdong Guangzhou 510030, China) |
| Abstract: | Objective：To explore the effect of DC885 and its mechanism on the invasion and migration of human nasopharyngeal carcinoma （NPC） cells.Methods：The effect of DC885 on the activity of AKT kinase was detected by AKT kinase assay kit in vitro.The effect of DC885 on cell viability was tested by MTT.The cell migration capability was determined by cell scratch assay.The cell invasion and migration abilities were determined by transwell chamber model.The expressions of AKT downstream targets,matrix metalloproteinases （MMPs） 2 and 9,EMT markers were detected by Western blotting.Results：DC885 inhibited the activity of AKT kinase in vitro and decreased the phosphorylation level of AKT downstream targets in NPC cells.1.25,2.5,5μmol/L DC885 had no obvious inhibitory effect on CNE-2-S-18 cells at 24 h.DC885 significantly inhibited the invasion and migration capabilities of NPC CNE-2-S-18 cells （H =15.025,P ＜ 0.01 in cell scratch assay,H =14.608,P ＜ 0.01 in transwell migration assay,H =14.980,P ＜ 0.01 in transwell invasion assay）.DC885 dose-dependently increased the expressions of E-cadherin,α-Catenin and decreased the expressions of MMP2,MMP9,Vimentin,Fibronectin.Conclusion：DC885 significantly inhibited invasion and migration of NPC CNE-2-S-18 cells.This mechanism may be involved in the inhibition of MMP2 and MMP9 expressions and reversal of EMT. |
| Keywords: | DC885 nasopharyngeal carcinoma migration invasion |
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