肝细胞生长因子对非小细胞肺癌侵袭和迁移的影响  

Hepatocyte growth factor influences proliferation and invasion of non-small cell lung cancer via targeting epithelial-mesenchymal transition

作　　者：李思文[1] 夏旭[1] 胡宁东[1] 罗国庆[1] 刘秋华[1] 赵健[2] 殷俊[2] 傅文凡[2] 

机构地区：[1]广州医科大学附属第六医院胸心一区,广东清远511500 [2]广州医科大学附属肿瘤医院肺肿瘤科,广东广州510095

出　　处：《广东医学》2017年第2期173-177,共5页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81501969);广州市医药卫生科技项目(编号:20142A011023)

摘　　要：目的探讨肝细胞生长因子(HGF)对非小细胞肺癌(NSCLC)转移的影响及其可能的分子机制。方法以HGF进行诱导培养NSCLC细胞株A549及其耐药株A549/DDP,应用Real time PCR及Western blot检测诱导前后细胞内上皮间质转化(EMT)相关标志物波形蛋白(vimentin)、钙黏蛋白E(E-cadhe-rin)表达的变化。将细胞种植在细胞培养板,设置未外源性添加HGF的为对照组,外源性添加HGF进行细胞培养的为HGF诱导组,应用细胞划痕以及Transwell实验检测诱导前后两株细胞迁移侵袭能力的变化。结果 HGF在A549/DDP细胞的mRNA表达水平较A549细胞显著升高,差异有统计学意义(P<0.05);提高A549/DDP及A549细胞微环境中HGF水平可诱导细胞vimentin增加、E-cadherin减少,差异均有统计学意义(基因水平P<0.01,蛋白水平P<0.05)。细胞划痕实验显示,A549/DDP细胞愈合较A549细胞快,差异有统计学意义(P<0.05),HGF诱导可使细胞侵袭能力增强;Transwell结果显示,HGF诱导组的A549/DDP、A549细胞相对未诱导前细胞的侵袭能力增强,差异均有统计学意义(均P<0.01)。结论 HGF促进NSCLC细胞A549/DDP及A549的侵袭迁移,其机制可能与通过调控EMT相关基因的表达相关。Objective To explore that how hepatocyte growth factor（ HGF） effects metastasis on lung cancer and its possible molecular mechanisms.Methods Non-small cell lung cancer（ NSCLC） cells were induced with HGF to established drug-resistance A549/DDP cell line.Real-time PCR and Western blot were applied to detect the expression of HGF on epithelial-mesenchymal transition（ EMT）-related markers,including Vimentin and E-cadherin,which in lung cancer cell lines A549 and A549/DDP with different drug-resistance.Cell wound scratch assay and Transwell assay were applied to evaluate the effects of HGF on A549/DDP and A549 cells＇ invasion and migration ability before and after the stimulation-induced.Results The expression of HGF in the lung cancer cell A549/DDP was（ 2.82 ± 0.23） times higher than that in A549 cells（ P〈0.05）.Improving the level of HGF on the cellular microenvironment in A549/DDP and A549 could stimulate the EMT makers Vimentin enhanced while E-cadherin descend,which the difference was statistically significant（ the genetic level P〈0.01,protein level P〈0.05）.The cell wound scratch assay showed that the scratch width of A549/DDP group was significantly higher than that in A549 group（ P〈0.05）.Transwell assay showed that the invasion ability of A549/DDP cells after inducing with HGF was significantly increased than A549 group（ P〈0.01）.Conclusion HGF increase invasion and migration ability of A549/DDP and A549 cells via regulationg the expression of EMT-related genes.

关 键 词：非小细胞肺癌 肝细胞生长因子 A549细胞 A549/DDP细胞 侵袭 迁移 上皮间质转化 

分 类 号：R734.2[医药卫生—肿瘤]