摘要
目的:研究吉非替尼在肺癌上皮细胞向间充质细胞转化(EMT)中的作用。方法:将24例肺腺癌行纤维支气管镜患者,取活检标本行H&E染色和Western,观察细胞形态和蛋白表达。将24只成年小鼠,植入LLC,随机挑选12只予吉非替尼灌胃,余12只作为对照组,观察肿瘤生长情况,病理切片观察细胞形态,Western观察E-Cadherin表达。结果 :在人群中发现有转移灶的患者,H&E染色有大量间质细胞形态倾向的肿瘤细胞,同时蛋白质组学提示,PDK1-Akt有活化,E-Cadherin表达较对照有降低。在动物实验中,发现吉非替尼组转移的肿瘤灶明显减少(P<0.05),细胞形态较对照组细胞显示较弱的倾袭形态;Western提示PDK1-Akt信号通路蛋白表达吉非替尼组有明显降低,吉非替尼组E-Cadherin表达降低。结论 :吉非替尼通过PDK1-Akt通路影响肺癌细胞E-Cadherin表达和EMT。
Objective To study the role of Gefitinih in EMT during tumor metastasis. Methods In population studies, biopsy specimens obtained via bronchoscopy from 24 patients with lung adenocarcinoma were analyzed by both H & E staining for cell morphology and Western Blot for protein expressions. In animal studies, 24 adult mice with LLC tumor eel1 implantation were equally divided randomly into the Gefitinib group and the control group. Grown tumors were seeded for further analyses including cell morphology, PDK1-Akt signaling and EMT-assoeiated protein expressions. Results In population studies, more mesenchymal cells were found in cases with more metastases. There was also elevated activation of PDK1-Akt signal pathway but lower expression of E- Cadherin in these cases. In animal studies, the Gefitinib group showed less metastases (P〈0.05), accompanied with weak invasive tumor cell morphology, decreased PDK1-Akt signaling and diminished E-Cadherin staining. Conclusion Gefitinib may block the expression of E-Cadherin and EMT in tumor cells through PDK1-Akt signaling pathway.
出处
《实用医学杂志》
CAS
北大核心
2015年第10期1566-1569,共4页
The Journal of Practical Medicine
基金
国家自然科学基金(编号:81200168)