[1]孙 洁,孔界男,刘 超,等.NVP-BEZ235抑制肝癌细胞HepG2的增殖和迁移及机制研究[J].中国药理学通报,2019,(08):1164-1171.[doi:10.3969/j.issn.1001-1978.2019.08.025]
 SUN Jie,KONG Jie-nan,LIU Chao,et al.Inhibitory effect of NVP-BEZ235 on proliferation and migration of hepatocellular carcinoma cell HepG2 and its mechanism[J].Chinese Pharmacological Bulletin,2019,(08):1164-1171.[doi:10.3969/j.issn.1001-1978.2019.08.025]
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NVP-BEZ235抑制肝癌细胞HepG2的增殖和迁移及机制研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年08期
页码:
1164-1171
栏目:
论著
出版日期:
2019-08-14

文章信息/Info

Title:
Inhibitory effect of NVP-BEZ235 on proliferation and migration of hepatocellular carcinoma cell HepG2 and its mechanism
文章编号:
1001-1978(2019)08-1164-08
作者:
孙 洁123孔界男4刘 超5林贞花123任香善123
延边大学1.肿瘤研究中心、2.医学院病理学教研室、3.吉林省科技厅重点实验室,吉林 延吉 133002; 4.大连医科大学附属第一医院病理科,辽宁 大连 116011; 5.延边大学附属医院神经内科,吉林 延吉 133000
Author(s):
SUN Jie123 KONG Jie-nan4 LIU Chao5 LIN Zhen-hua123 REN Xiang-shan123
1.Cancer Research Center, 2.Dept of Pathology, Medical College, 3.Key Lab of the Science and Technology Dept of Jilin Province,Yanbian University, Yanji Jilin 133002, China; 4.Dept of Pathology, the First Affiliated Hospital of Dalian Medical University,Dalian Liaoning 116011, China; 5.Dept of Neurology, Affiliated Hospital of Yanbian University, Yanji Jilin 133000, China
关键词:
NVP-BEZ235 肝癌 增殖 迁移 Six1/Ezrin 上皮-间质转化
Keywords:
NVP-BEZ235 hepatocellular carcinoma proliferation migration Six1/Ezrin EMT
分类号:
R329.24; R394.2; R73-35; R735.702.2; R916.4
DOI:
10.3969/j.issn.1001-1978.2019.08.025
文献标志码:
A
摘要:
目的 探究NVP-BEZ235对肝癌细胞HepG2增殖和迁移的影响及其机制。方法 NVP-BEZ235(0、25、50、100、250、500 nmol·L-1)处理HepG2细胞48 h后,采用MTT法检测细胞的活性; 通过形态学观察和Hoechst 33342染色法,检测NVP-BEZ235对HepG2细胞增殖、凋亡的影响; 采用划痕实验、Transwell迁移实验,检测NVP-BEZ235对HepG2细胞迁移能力的影响; 免疫印迹法检测PI3K/Akt/mTOR信号通路、上皮-间质转化(EMT)以及Six1/Ezrin信号轴等标志物的表达情况; 采用免疫荧光实验检测EMT相关标志物的表达情况。结果 NVP-BEZ235可明显抑制HepG2细胞的增殖,且呈浓度依赖性; NVP-BEZ235可诱导HepG2细胞发生凋亡; NVP-BEZ235可抑制HepG2细胞的迁移能力。在NVP-BEZ235的作用下,p-AktSer473、p-S6Thr389、p-4E-BP1Thr37/46的表达下调,上皮标志物E-cadherin表达上调,间质标志物Vimentin、Snail表达下调,Six1和p-EzrinTyr353表达下调。结论 NVP-BEZ235可有效抑制HepG2细胞的增殖和迁移,其机制可能与NVP-BEZ235降低p-AktSer473、p-S6Thr389、p-4E-BP1Thr37/46的表达,抑制Six1/Ezrin信号轴及逆转EMT的进程有关。
Abstract:
Aim To evaluate the efficacy of NVP-BEZ235 on the proliferation and migration of HepG2 human hepatocellular carcinoma cell in vitro, and to investigate the molecular mechanism.Methods The cytotoxicity of NVP-BEZ235 on HepG2 cells treated with NVP-BEZ235(0, 25, 50, 100, 250, 500 nmol·L-1)was detected by MTT assay.The ability of NVP-BEZ235 to modulate HepG2 cells proliferation and apoptosis was detected by morphology assay and Hoechst 33342 staining.The motility of NVP-BEZ235 treatment on HepG2 cells was determined by wound healing assay and Transwell assay.The expression levels of the related protein including PI3K/Akt/mTOR signal pathway, epithelial-mesenchymal transition(EMT)process and Six1/Ezrin signal axis were detected by Western blot.The expression levels of EMT markers were also detected by immunofluorescence staining.Results The cell viability significantly decreased in HepG2 cells treated with NVP-BEZ235 compared with control group, which showed a dose-dependent manner.NVP-BEZ235 could induce apoptosis and inhibit HepG2 cell migration.E-cadherin protein expression significantly increased; however, the expressions of p-AktSer473, p-S6Thr389, p-4E-BP1Thr37/46, Vimentin, Snail, Six1 and p-EzrinTyr353 decreased in NVP-BEZ235 treated HepG2 cells compared with those in control group.Conclusions NVP-BEZ235 could effectively suppress the proliferation and migration of HepG2 cells, which may be related to the down-regulation of p-AktSer473, p-S6Thr389, p-4E-BP1Thr37/46 and modulating both Six1/Ezrin signal axis and the EMT process by NVP-BEZ235 treatment.

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备注/Memo

备注/Memo:
收稿日期:2019-03-11,修回日期:2019-04-19
基金项目:国家自然科学基金地区基金项目(No 31760313); 吉林省科技发展计划项目(No 20180101007JC); 吉林省科技厅重点实验室基金(No 20170622007JC)
作者简介:孙 洁(1985-),女,博士生,研究方向:肿瘤分子病理学, E-mail:82300428@qq.com;
任香善(1976-),女,博士,副教授,硕士生导师,研究方向:肿瘤分子病理学,通讯作者,E-mail:renxsh@ybu.edu.cn
更新日期/Last Update: 2019-08-14