细胞间粘附在肺腺癌细胞株A549群集耐药中作用探讨  

Mechanisms of cell-cell adhesion dependent multicellular drug resistance of pulmonary adenocarcinoma cell line A549

作　　者：何建明[1] 梁后杰[1] 边志衡[1] 胡绍毅[1] 

机构地区：[1]第三军医大学西南医院肿瘤科,重庆400038

出　　处：《第三军医大学学报》2004年第24期2182-2184,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目 ( 30 1710 6 7)~~

摘　　要：目的　检测肺腺癌细胞株A5 49单层培养与三维培养时对阿霉素 (adriamycin ,ADM)药物敏感性的差异 ,并探讨细胞间粘附在肺腺癌群集耐药 (multicellulardrugresistance)中可能的作用机制。方法　以多细胞球 (multicellularspheroids ,MCSs)为模型 ,比较MCSs与单层细胞 (monolayercells ,MCs)对ADM药物敏感性的差异。透射电镜观察细胞超微结构。间接免疫荧光法流式细胞术检测Bcl 2 ,Bcl xL ,Bax的表达。结果　MCSs由多层细胞组成 ,细胞间粘附广泛而紧密 ;可见镶嵌连接。与MCs相比 ,MCSs的药物敏感性显著减弱。MCSs的Bcl 2 ,Bcl xL表达量显著高于MCs ,ADM处理后表达显著升高。结论　MCSs能够较好地模拟体内实体瘤的细胞间粘附 ,具有群集耐药性 ;其机制可能与Bcl xL ,Bcl 2高表达相关。Objective To study the mechanism of multicellular drug resistance of pulmonary adenocarcinoma cell line A549 mediated by cell-cell adhesion. Methods We compared the sensitivity of monolayer cells (MCs) to adriamycin (ADM) with that of multicellular spheroids (MCSs) which was employed as a three dimensional cell culture model. Transmission electron microscopy was applied to observe the cellular ultrastructure. Bcl-2, Bcl-xL, and Bax expression levels were detected by flow cytometry and indirect immunofluorescent staining. Results Compared with MCs, MCSs had more than two layers of cells, more extensive and compact cell adhesion, and inlay junctions were found within them. MCSs were more resistant to ADM. At the same time, Bcl-2 and Bcl-xL expressions in MCSs were much higher. After treatment with ADM, expressions Bcl-2 and Bcl-xL increased markedly in MCSs. Conclusion MCSs could simulate the solid tumors in vivo and has multicellular drug resistance mediated by cell-cell adhesion. The possible mechanisms may be associated with the upregulation of Bcl-2 and Bcl-xL.

关 键 词：肿瘤 耐药 

分 类 号：R73-354[医药卫生—肿瘤] R734.2[医药卫生—临床医学]