摘要
目的:探讨p21激活激酶2(PAK2)在非小细胞肺癌(NSCLC)中是否存在异常表达,以及是否影响肺癌细胞的顺铂敏感性。方法:采用免疫组化和Western blot(WB)方法检测NSCLC中PAK2的蛋白表达模式。利用PAK2-siRNA下调肺癌细胞系中PAK2的表达后,通过WB和细胞功能学实验等方法,明确PAK2对NSCLC细胞系增殖和侵袭能力的影响,并检测顺铂耐药前后的肺癌细胞系中PAK2的表达改变,及其对肺癌细胞顺铂敏感性的影响。结果:PAK2在NSCLC中呈现明显的胞浆强表达,并且其异常表达与肺癌的恶性表型相关;PAK2在顺铂耐药肺癌细胞中表达增强,抑制ERK活性后,PAK2的表达上调不能显著促进肺癌细胞对顺铂耐药。结论:PAK2在NSCLC中发挥着重要的促癌基因功能,并通过调节ERK信号通路的活性介导肺癌细胞系对顺铂耐药性。
Objective:To investigate the expression pattern of p21 activated kinase 2(PAK2)in non-small cell lung cancer(NSCLC)and its effect on the proliferation and invasion of lung cancer cells.Methods:The protein expression level of PAK2 in NSCLC was detected by immunohistochemistry and Western blot(WB).PAK2-siRNA was used to down-regulate the expression of PAK2 in lung cancer cell lines.We revealed the effects of PAK2 on the cell malignant phenotype and the possible molecular regulation mechanisms via WB and cell function experiments.In the process of inducing the erlotinib resistance of lung cancer cell lines,the expression level of PAK2 and its effect on erlotinib sensitivity were also detected.Results:Compared with normal lung tissues,PAK2 showed strong cytoplasmic expression in NSCLC,and its abnormal expression was correlated with low differentiation(P=0.014),high TNM stage(P=0.011)and lymph node metastasis(P=0.040).In lung cancer cell lines,PAK2 down-regulation significantly inhibited the proliferation(P<0.05)and invasion(P<0.05)of lung cancer cells by inhibiting the activity of ERK signaling pathway.Furthermore,PAK2 down-regulation promote the sensitivity of lung cancer cells to erlotinib.Conclusion:PAK2 plays an important role in promoting oncogene function in NSCLC,and plays an important role in mediating drug resistance of NSCLC,which is expected to provide scientific basis for seeking individualized treatment of NSCLC.
作者
王爽
荣雪竹
王斯
李珍
刘洋
WANG Shuang;RONG Xuezhu;WANG Si;LI Zhen;LIU Yang(Department of Anesthesiology,The First Hospital of China Medical University,Liaoning Shenyang 110001,China;Department of Pathology,The First Hospital of China Medical University,Liaoning Shenyang 110001,China;Department of Medical Microbiology and Human Parasitology,Basic Medicine College,China Medical University,Liaoning Shenyang 110122,China)
出处
《现代肿瘤医学》
CAS
北大核心
2023年第13期2448-2454,共7页
Journal of Modern Oncology
基金
国家自然科学基金(编号:82003119)
辽宁省教育厅高校基本科研项目(编号:LJKZ0763)。