中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (1): 43-49.doi: 10.19401/j.cnki.1007-3639.2018.01.006

• 论著 • 上一篇    下一篇

Lyn激酶对肺腺癌EGFR下游信号通路的调节作用研究

戴 曦1,2,李国平1,3,杨小琼1,王孝芸4,伍 娟5,梁丽娴2   

  1. 1. 西南医科大学附属医院呼吸内一科,四川 泸州 646000 ;
    2. 澳门科技大学中药质量研究国家重点实验室/ 澳门药物与健康应用研究院,澳门特别行政区 999078 ;
    3. 成都市第三人民医院/ 西南交通大学附属医院呼吸内科,四川 成都 610000 ;
    4. 西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000 ;
    5. 四川省第二中医医院呼吸内科,四川 成都 610000
  • 出版日期:2018-01-30 发布日期:2018-02-07
  • 通信作者: 梁丽娴 E-mail:lhleung@must.edu.mo
  • 基金资助:
    西南医科大学科研项目(2015-YJ085)。

Effects of Lyn kinase on EGFR signaling pathway in lung adenocarcinoma

DAI Xi1,2, LI Guoping1,3, YANG Xiaoqiong1, WANG Xiaoyun4, WU Juan5, LEUNG Laihan2   

  1. 1. Department of Respiratory, Affiliated Hospital of South West Medical University, Luzhou 646000, Sichuan Province, China; 2. State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR 999078, China; 3. Department of Respiratory, the Third People’s Hospital of Chengdu/Affiliated Hospital of Southwest Jiao Tong University, Chengdu 610000, Sichuan Province, China; 4. Inflammation and Allergy Laboratory, Affiliated Hospital of South West Medical University, Luzhou 646000, Sichuan Province, China; 5. Department of Respiratory, the Second Chinese Medicine Hospital of Sichuan Province, Chengdu 610000, Sichuan Province, China
  • Published:2018-01-30 Online:2018-02-07
  • Contact: LEUNG Laihan E-mail: lhleung@must.edu.mo

摘要: 背景与目的:目前,酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)应用于存在表皮生长因子受体(epithelial growth factor receptor,EGFR)突变的患者虽然取得了重大突破,但大约70%的患者仍难以避免地出现TKI耐药,治疗效果不尽人意。本研究通过研究Lyn激酶对EGFR突变肺腺癌细胞株的调节作用,探讨Lyn激酶对EGFR下游信号通路的影响,以期寻找新的分子靶点,提高肺癌的临床诊治水平。方法:采用慢病毒转染方法构建Lyn激酶高表达的EGFR突变细胞株Hcc827(Hcc827-Lyn+/+),通过裸鼠荷瘤实验、MTT实验、克隆实验、侵袭实验及蛋白[质]印迹法(Western blot),检测高表达Lyn激酶的Hcc827细胞株移植于裸鼠皮下后的生长状况,以及Lyn激酶高表达Hcc827细胞株在体外培养时增殖、克隆、侵袭能力及EGFR下游信号通路相关蛋白的表达水平。结果:与Hcc827细胞株比较,Hcc827-Lyn+/+细胞株在裸鼠荷瘤实验中表现出更强的增殖能力,但各组荷瘤裸鼠均未见明显远处转移。体外培养时,Hcc827-Lyn+/+细胞株增殖、克隆及侵袭能力强于Hcc827细胞株。Hcc827-Lyn+/+细胞株EGFR及其下游PI3K/AKT、JAK/STAT信号通路相关蛋白表达上调。结论:Lyn激酶高表达能通过EGFR下游信号通路上调EGFR突变肺腺癌细胞株的增殖、侵袭能力。

关键词: Lyn激酶, 肺腺癌, 表皮生长因子受体, 裸鼠, 增殖, 侵袭

Abstract: Background and purpose: The application of tyrosine kinase inhibitor (TKI) in lung cancer patients with epidermal growth factor receptor (EGFR) mutations has been a significant breakthrough recently. However, almost 70% patients would suffer from TKI drug resistance inevitably so that the treatment effect is unsatisfactory. In order to look for new molecular target for improving the level of clinical diagnosis and treatment of lung cancer, this study aimed to investigate the regulatory effects of Lyn kinase on cell line with EGFR mutation and the influence of Lyn kinase on EGFR downstream signaling pathway. Methods: The lentiviral vector expressing Lyn was used to construct the Lyn kinase high expression Hcc827 cell lines (Hcc827-Lyn+/+). By means of tumor bearing experiment in nude mice, MTT experiment, cloning experiment, invasion experiment and Western blot method, we detected the ability of proliferation, cloning and invasion of high Lyn kinase expression Hcc827 cell lines and expression level of EGFR signaling pathway related proteins. Results: Compared with Hcc827 cell lines, Hcc827- Lyn+/+ cell lines showed stronger ability of proliferation in nude mice tumor bearing experiment. However, there was no distant metastasis in any nude mouse. Results of in vitro culture showed Hcc827-Lyn+/+ cell lines had stronger ability of proliferation, cloning and invasion compared with Hcc827 cell lines. The related proteins of EGFR and its downstream signaling pathway were upregulated in Hcc827-Lyn+/+ cell lines. Conclusion: High expression of Lyn kinase can promote the proliferation, cloning and invasion ability of Hcc827 cell lines. These effects are achieved by EGFR signaling pathway upregulation.

Key words: Lyn kinase, Lung adenocarcinoma, Epidermal growth factor receptor, Nude mice, Proliferation, Invasion