Ehrlich P H, Moustafa Z A, Archinal-Mattheis A E, Newman M J, Bair K W, Cohen D
Oncology Research Program, Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, East Hanover, NJ 07936, USA.
Anticancer Res. 1997 Jan-Feb;17(1A):129-33.
Multidrug resistance (MDR) is a major impediment to the effective treatment of cancer. We have used multicellular tumor spheroids (MTS) as a model to investigate whether MDR can be reversed in a three dimensional structure. MTS are tightly associated aggregates of tumor cells that exhibit many of the properties of solid tumors. A human MDR breast carcinoma cell line was selected by exposure to taxol under monolayer conditions. The sensitive (parental) and drug-resistant phenotypes were retained when the cells were grown as MTS. Thus, the three dimensional conditions in this novel model system did not affect the MDR phenotype. SDZ PSC 833 is an efficient MDR reversing agent as determined under monolayer conditions and is currently being evaluated in clinical trials. Resistance to taxol and doxorubicin of the MDR cells grown as MTS was almost completely reversed by SDZ PSC 833. Our results suggest that SDZ PSC 833 has the potential to reverse the MDR phenotype in solid tumors.
多药耐药性（MDR）是有效治疗癌症的主要障碍。我们使用多细胞肿瘤球体（MTS）作为模型来研究在三维结构中MDR是否可以被逆转。MTS是紧密相连的肿瘤细胞聚集体，具有实体瘤的许多特性。通过在单层培养条件下暴露于紫杉醇来选择一株人MDR乳腺癌细胞系。当细胞以MTS形式生长时，敏感（亲本）和耐药表型得以保留。因此，这个新型模型系统中的三维条件并未影响MDR表型。SDZ PSC 833在单层培养条件下被确定为一种有效的MDR逆转剂，目前正在进行临床试验评估。作为MTS生长的MDR细胞对紫杉醇和阿霉素的耐药性几乎被SDZ PSC 833完全逆转。我们的结果表明，SDZ PSC 833有可能逆转实体瘤中的MDR表型。
