摘要
目的:探究唑来膦酸对肿瘤相关巨噬细胞(TAMs)表型转化和HGF表达的作用及对肺癌细胞增殖和耐药的影响。方法:通过Transwell系统将M2巨噬细胞与小鼠肺癌细胞Lewis共培养,得到M2型TAM(M2-TAMs)。采用不同浓度唑来膦酸作用于M2-TAMs,采用ELISA和RT-PCR检测M1型标记(IL-1β、TNFα、IL-6和iNOS)、M2型标记(HGF、EGF、IL-10和Arg1)的表达改变,采用Western blot检测NF-κB的表达。建立Transwell M2-TAMs-Lewis共培养模型,采用MTT方法检测肿瘤细胞的增殖和对吉非替尼耐药的影响;采用NF-κB特异性抑制剂PDCT作用唑来膦酸处理的TAMs,进一步检测TAMs M1/M2表型改变。结果:随着唑来膦酸浓度的增加,TAMs M1表型显著增强,M2表型逐渐减弱;与对照组相比,唑来膦酸处理的TAMs显著抑制了肺癌细胞的增殖,增强了其对吉非替尼的敏感性。在NF-κB特异性抑制剂(PDTC)的作用下,唑来膦酸处理的TAMs M1表型减弱,而M2表型增强。结论:唑来膦酸通过活化NF-κB信号通路促进肿瘤相关巨噬细胞M1表型转化并抑制肺癌细胞的增殖和耐药。
Objective:To investigate the effects of zoledronic acid on phenotype transformation of tumor-associated macrophages(TAMs),expression of HGF and proliferation and drug resistance of lung cancer cells.Methods:M2-TAMs were obtained by co-culture of M2 macrophages with Lewis cells of mouse lung cancer cells through Transwell system.Different concentrations of zoledronic acid were used to treat M2-TAMs.The expression of M1 markers(IL-1β,TNFα,IL-6 and iNOS),M2 markers(HGF,EGF,IL-10 and Arg1)were detected by ELISA and RT-PCR.Western blot was used to detect the expression of NF-κB.Transwell M2-TAMs-Lewis co-culture model was established.MTT method was used to detect the effects of proliferation of tumor cells and the influence of proliferation of tumor cells on gefitinib resistance.The phenotypic changes of TAMs M1/M2 were further detected under the effect a specific inhibitor of NF-κB,PDTC.Results:With the increase of zoledronic acid concentration,TAMs M1 phenotype increased significantly and M2 phenotype weakened gradually.Compared with the control group,zoledronic acid-treated TAMs significantly inhibited the proliferation of lung cancer cells and enhanced their sensitivity to gefitinib.Under the action of NF-κB specific inhibitor,the phenotype of TAMs M1 treated with zoledronic acid decreased while that of M2 increased.Conclusion:Zoledronic acid promotes M1 phenotype transformation of tumor-associated macrophages and inhibits the proliferation and drug resistance of lung cancer cells by activating NF-κB signaling pathway.
作者
杨超
刘贝
魏微
胡芬
姚洋
孙志华
YANG Chao;LIU Bei;WEI Wei;HU Fen;YAO Yang;SUN Zhihua(Xiangyang Central Hospital,Affiliated Hospital of Hubei University of Arts and Sciences,Hubei Xiangyang 441000,China)
出处
《现代肿瘤医学》
CAS
北大核心
2021年第22期3895-3901,共7页
Journal of Modern Oncology
基金
CSCO临床肿瘤学研究项目(编号:Y-HS2019/2-017)。