吉林大学学报(医学版) ›› 2021, Vol. 47 ›› Issue (5): 1131-1138.doi: 10.13481/j.1671-587X.20210508

• 基础研究 • 上一篇    下一篇

胰岛素样生长因子1受体抑制剂NVP-AEW541对ESCC细胞增殖、迁移和侵袭的影响及其机制

曹雅杰1,包晓红2,李书珍1,耿海营1,蔡曾晓瑞1,代春美3,李宁1,4,5()   

  1. 1.锦州医科大学基础医学院生物化学与分子生物学教研室,辽宁 锦州 121001
    2.台州学院医学院基础医学部细胞生物学学科,浙江 台州 318000
    3.锦州医科大学药物研究所,辽宁 锦州 121001
    4.锦州医科大学生物人类学研究所,辽宁 锦州 121001
    5.辽宁省人类表型组重点研究实验室,辽宁 锦州 121001
  • 收稿日期:2021-01-19 出版日期:2021-09-28 发布日期:2021-10-26
  • 通讯作者: 李宁 E-mail:157026753@qq.com
  • 作者简介:曹雅杰(1996-),女,山东省烟台市人,在读硕士研究生,主要从事食管癌基础方面的研究。
  • 基金资助:
    国家自然科学基金项目(31400646);辽宁省教育厅服务地方项目(JYTFW201915);辽宁省高等学校创新人才资助项目(LR2019028);辽宁省大学生创新创业训练计划项目(201810160001);锦州医科大学生物人类学创新团队开放课题项目(JYLJ201702)

Effects of insulin-like growth factor 1 receptor inhibitor NVP-AEW541 on proliferation, migration and invasion of ESCC cells

Yajie CAO1,Xiaohong BAO2,Shuzhen LI1,Haiying GENG1,Zengxiaorui CAI1,Chunmei DAI3,Ning LI1,4,5()   

  1. 1.Department of Biochemistry and Molecular Biology,College of Basic Medical Sciences,Jinzhou Medical Unversity,Jinzhou 121000,China
    2.Department of Cell Biology,College of Basic Medical Sciences,School of Medical Sciences,Taizhou University,Taizhou 318000,China
    3.Institute of Materia Medica,Jinzhou Medical University,Jinzhou 121001,China
    4.Institute of Biological Anthropology,Jinzhou Medical University,Jinzhou 121001,China
    5.Key Research Laboratory of Human Phenotype Group of Liaoning Province,Jinzhou 121001,China
  • Received:2021-01-19 Online:2021-09-28 Published:2021-10-26
  • Contact: Ning LI E-mail:157026753@qq.com

摘要: 目的

探讨胰岛素样生长因子1受体(IGF-1R)抑制剂NVP-AEW541对3种食管鳞状细胞癌(ESCC)细胞KYSE30、KYSE450和TE-1增殖、迁移和侵袭的影响,初步阐明其作用机制。

方法

体外培养的KYSE30、KYSE450和TE-1 ESCC细胞作为实验对象,分为对照组[0 μmol·L-1 NVP-AEW541,1 mL RPMI 1640完全培养基+1 μL 二甲亚砜(DMSO)]和实验组(2、4、6、8和10 μmol·L-1 NVP-AEW541),对照组和实验组细胞处理48 h后,CCK-8法检测各组细胞存活率;对照组和实验组(4和6 μmol·L-1 NVP-AEW541)细胞处理0、6、12和24 h后,细胞划痕实验检测各组细胞迁移率;对照组和实验组(6 μmol·L-1 NVP-AEW541)细胞处理48 h后,Transwell实验检测侵袭细胞数;对照组和实验组(2、4和6 μmol·L-1 NVP-AEW541)细胞处理48 h后,Western blotting法检测各组细胞中磷酸化IGF-1R(p-IGF-1R)和上皮-间质转化(EMT)相关蛋白N-Cadherin和Snail-1的蛋白表达水平。

结果

与对照组比较,实验组KYSE30、KYSE450和TE-1细胞存活率均随NVP-AEW541浓度增加而降低(P<0.05),实验组(10 μmol·L-1)KYSE30、KYSE450和TE-1细胞存活率明显降低(P<0.01),实验组(6 μmol·L-1)KYSE30、KYSE450和TE-1细胞迁移率随NVP-AEW541浓度增加而降低(P<0.01),实验组(6 μmol·L-1)KYSE30、KYSE450和TE-1细胞侵袭细胞数明显减少(P<0.01),且实验组细胞中p-IGF-1R、N-Cadherin和Snail-1蛋白的表达水平均明显降低(P<0.01)。

结论

NVP-AEW541能够明显抑制ESCC细胞增殖,通过抑制N-Cadherin和Snail-1蛋白表达,阻碍EMT,抑制ESCC细胞迁移和侵袭。

关键词: NVP-AEW541, 食管鳞癌细胞, 细胞增殖, 细胞迁移, 细胞侵袭

Abstract: Objective

To explore the effects of insulin-like growth factors-1 receptor NVP-AEW541 on the proliferation, migration and invasion of three kind of esophageal squamous cell carcinoma (ESCC) cells KYSE30, KYSE450 and TE-1, and to preliminarily clarify their mechanisms.

Methods

The ESCC cells KYSE30, KYSE40 and TE-1 cultured in vitro were used as experimental subjects and divided into control group (0 μmol·L-1 NVP-AEW541,1 mL RPMI 1640 complete medium + 1 μL DMSO) and experimental groups(2, 4, 6, 8 and 10 μmol·L-1 NVP-AEW541).After the cells in control group and experimental group were treated for 48 h, CCK-8 assay was used to detect the cell survival rates in various groups; after the cells in control group and experimental groups (4 and 6 μmol·L-1 NVP-AEW541)were treated for 0, 6, 12 and 24 h, cell scratch test was used to detect the cell migration rates in various groups; after the cells in control group and experimental group (6 μmol·L-1 NVP-AEW541) were treated for 48 h, Transwell test was to used detect the number of invasion cells in various groups; after the cells in control group and experimental groups (2, 4 and 6 μmol·L-1 NVP-AEW541) were treated for 48 h, Western blotting method was used to detect the expression levels of p-IGF-1R and epithelial-mesenchymal transition (EMT)-related proteins N-Cadherin and Snail-1 proteins in the cells in various groups.

Results

Compared with control group, the cell survival rates of KYSE30, KYSE450 and TE-1 cells in experimental groups were decreased with the increase of the concentration of NVP-AEW541 (P<0.05); the survival rates of KYSE30, KYSE450 and TE-1 cells in experimental group (10 μmol·L-1) were decreased(P<0.01); the cell migration rates in experiment group (6 μmol·L-1) were decreased with the increase of NVP-AEW541 concentration (P<0.01); the number of invasion cells in experimental group (6 μmol·L-1) was decreased (P<0.01); the expression levels of p-IGF-1R,N-Cadherin and Snail-1 proteins in the cells in experimental group were significantly decreased (P<0.01).

Conclusion

NVP-AEW541 can significantly inhibit the proliferation of ESCC cells,by inhibiting the expressions of N-Cadherin and Snail-1 proteins, it prevents the EMT, and inhibit the migration and invasion of ESCC cells.

Key words: NVP-AEW541, esophageal squamous cell carcinoma, cell proliferation, cell migration, cell invasion

中图分类号: 

  • R735.1