Mechanisms of cell-cell adhesion dependent multicellular drug resistance of pulmonary adenocarcinoma cell line A549 / 第三军医大学学报

ABSTRACT

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.