整合素连接激酶在非小细胞肺癌中过度表达及促进肺癌细胞的侵袭和迁移

摘要

目的：探讨整合素连接激酶（ILK）在非小细胞肺癌（NSCLC）中的表达及在侵袭和迁移中的作用和相关分子机制。方法：免疫组化法检测 ILK 蛋白在 NSCLC 患者中的表达，细胞转染、siRNA 干扰、细胞划痕试验、实时定量 PCR、Western blot 方法探讨 ILK 在肺癌 A549细胞中的表达及分子机制。结果：ILK 蛋白在原发性 NSCLC 组织中过度表达30.6%（33/108）并且和 TNM 分期（P ＝0.001）、淋巴结转移（ P ＝0.033）相关。ILK 在 A549细胞中过度表达并且通过下调 E - cadherin，上调波形蛋白、纤维连接蛋白、Snail、Slug 导致上皮-间质转化（EMT）。此外，NF -κB 抑制剂 BAY 11-7028和小干扰靶 RNA（siRNA）NF - P65可诱导 E - cadher-in 的表达下调。结论：ILK 在原发性 NSCLC 组织中高表达并与 TNM 分期和淋巴结转移相关，其促进肺癌细胞的侵袭和迁徙机制可能是经 NF -κB 信号通路诱导 EMT 所致。%Objective:To detect the exPression of integrin - linked kinase(ILK)in non - small cell lung cancer (NSCLC)and investigate the molecular mechanism in invasion and migration. Methods:The exPression of ILK was determined by means of immunohistochemistry in Patients with NSCLC. The exPression and molecular mechanism of ILK in A549 cells were studied by cell transfection,siRNA interference,cell scratch test,real - time quantitative PCR and Western blot. Results:The exPression rate of ILK was 30. 6%(33 / 108)in Primary NSCLC tissue that was asso-ciated with TNM staging(P = 0. 001)and lymPh node metastasis(P = 0. 033). ILK was over - exPressing in A549 cells and led to ePithelial mesenchymal transition(EMT)through down - regulating E - cadherin,uP - regulating vi-mentin,fibronectin,Snail and Slug. In addition,NF - κB inhibitor BAY 11 - 7028 and small interference target RNA (siRNA)NF - P65 could induce the down - regulation of E - cadherin. Conclusion:ILK was over - exPressed in NSCLC and associated with TNM staging and lymPh node metastasis. ILK Promotes lung cancer cell migration and in-vasion by inducing EMT through NF - κB signal Pathway.