Kolchinsky A, Roninson I B
Department of Genetics (M/C 669), University of Illinois at Chicago 60612, USA.
Anticancer Res. 1997 Sep-Oct;17(5A):3321-7.
Three-dimensional cell cultures (spheroids) provide an in vitro approximation of solid tumors in vivo. Some mechanisms of drug resistance were reported to differ in their effects on monolayer and spheroid cells. We have compared the effect on the expression of P-glycoprotein (Pgp), the MDR1 gene product, on vinblastine resistance in two glioblastoma lines, U87 and U251, grown as either monolayers or spheroids. U87 cells form spheroids spontaneously and the spheroids continue to grow, while U251 cells form spheroids only when plated over agarose and do not proliferate in spheroids. U87 cells are equally resistant to vinblastine in monolayer and in spheroids, while U251 cells are 4.5 times more resistant in spheroids than in monolayers. The distribution of a fluorescent vinblastine derivative in cells of spheroids was more heterogeneous than in monolayers. MDR1-expressing U87 cells increased their resistance 9-fold in monolayer and 50-fold in spheroids, while MDR1 transduction of U251 cells made them 20-fold more resistant in monolayer and 160-fold more resistant in spheroids. MDR1 expression in both cell lines decreased the accumulation of 3H-vinblastine and fluorescent vinblastine derivative. These results indicate that MDR1 is more efficient in conferring drug resistance in spheroids than in monolayer cells.
三维细胞培养（球体）提供了体内实体瘤的体外近似模型。据报道，一些耐药机制对单层细胞和球体细胞的影响有所不同。我们比较了在两种胶质母细胞瘤细胞系U87和U251中，作为单层细胞或球体生长时，P-糖蛋白（Pgp，MDR1基因产物）的表达对长春碱耐药性的影响。U87细胞能自发形成球体且球体持续生长，而U251细胞只有接种在琼脂糖上时才形成球体，且在球体中不增殖。U87细胞在单层培养和球体培养时对长春碱的耐药性相同，而U251细胞在球体培养时的耐药性比单层培养时高4.5倍。荧光长春碱衍生物在球体细胞中的分布比在单层细胞中更不均匀。表达MDR1的U87细胞在单层培养时耐药性增加9倍，在球体培养时增加50倍，而U251细胞经MDR1转导后，在单层培养时耐药性增加20倍，在球体培养时增加160倍。两种细胞系中MDR1的表达均降低了3H-长春碱和荧光长春碱衍生物的积累。这些结果表明，MDR1在赋予球体细胞耐药性方面比单层细胞更有效。
