肿瘤干细胞标志物DCLK1通过AKT信号通路促进鼻咽癌细胞的生长与转移  

Tumor Stem Cell Marker DCLK1 Promotes the Growth and Metastasis of Nasopharyngeal Carcinoma Cells Through the AKT Signaling Pathway

作　　者：刘伟[1] 代伟林 王英杰 黄晶 Liu Wei;Dai Weilin;Wang Yingjie(Department of Otorhinolaryngology Head and Neck Surgery,Wuhan Hospital of Traditional Chinese and Western Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属武汉中西医结合医院耳鼻咽喉头颈外科,武汉430022 [2]华中科技大学同济医学院附属协和医院肿瘤中心,武汉430023

出　　处：《华中科技大学学报（医学版）》2022年第4期456-460,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2013CFB103)。

摘　　要：目的探究肿瘤干细胞标志物DCLK1在鼻咽癌中的表达及生物学功能。方法通过免疫蛋白质印迹、qPCR和免疫组织化学法检测了DCLK1在鼻咽癌细胞株和鼻咽癌临床组织标本中的表达;通过细胞计数、克隆形成及细胞迁移实验检测DCLK1在体外对鼻咽癌细胞增殖与迁移的影响;通过裸鼠移植瘤和尾静脉注射实验检测DCLK1在体内对鼻咽癌细胞生长与转移的影响。结果DCLK1在鼻咽癌细胞株和临床组织标本中均高表达。体外实验表明,敲低DCLK1表达可抑制鼻咽癌CNE1细胞的增殖、克隆形成及肿瘤细胞迁移。在裸鼠皮下移植瘤模型中,敲低DCLK1表达可抑制鼻咽癌CNE1细胞生长;在裸鼠尾静脉转移模型中,敲低DCLK1表达可减少鼻咽癌CNE1细胞肺转移瘤形成。应用AKT抑制剂(AKT-IN-1)可阻断DCLK1促进鼻咽癌细胞生长与转移的生物学功能。结论DCLK1能通过AKT信号通路促进鼻咽癌的生长与转移,有望成为鼻咽癌潜在的治疗靶点。Objective The expression and biological functions of DCLK1 in nasopharyngeal carcinoma will be explored.Methods The expression levles of DCLK1 in nasopharyngeal carcinoma cell lines and clinical tissues were detected by Western blotting,qPCR and immunohistochemistry.The effects of DCLK1 on the proliferation and metastasis of nasopharyngeal carcinoma cells in vitro were detected by cell proliferation,colony formation and cell migration experiments.The effects of DCLK1 on the growth and metastasis of nasopharyngeal carcinoma cells in vivo were tested in mice.Results DCLK1 was found to be highly expressed in both nasopharyngeal carcinoma cell lines and clinical tissue specimens.In vitro experiments showed that knockdown of DCLK1 expression could inhibit proliferation,colony formation and tumor cell migration of nasopharyngeal carcinoma CNE1 cells.In vivo experiments showed that knockdown of DCLK1 expression could inhibit the growth of nasopharyngeal carcinoma CNE1 cells in subcutaneous transplanted tumor model of nude mice.In nude mice model of caudal vein metastasis,knockdown of DCLK1 expression could reduce lung metastasis of nasopharyngeal carcinoma CNE1 cell.Further study showed that DCLK1 upregulated the AKT signaling pathway.Application of AKT inhibitor(AKT-IN-1)could inhibit the biological function of DCLK1 in promoting the growth and metastasis of nasopharyngeal carcinoma cells.Conclusion DCLK1 promotes growth and metastasis of nasopharyngeal carcinoma through AKT signaling pathway,and may become a potential therapeutic target for nasopharyngeal carcinoma.

关 键 词：鼻咽癌 DCLK1 AKT信号通路 增殖 转移 

分 类 号：R739.63[医药卫生—肿瘤]