Drug resistance conferred by MDR1 expression in spheroids formed by glioblastoma cell lines.
Drug resistance conferred by MDR1 expression in spheroids formed by glioblastoma cell lines.
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发表时间：
1997-09
影响因子：
2
通讯作者：
A. Kolchinsky;Roninson Ib
中科院分区：
文献类型：
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作者：
A. Kolchinsky;Roninson Ib
三维细胞培养物（球状体）提供了体内实体瘤的体外近似。据报道，一些耐药机制在单层和球状体细胞上的作用不同。我们已经比较了P-糖蛋白（Pgp），MDR 1基因产物，长春碱耐药的两个胶质母细胞瘤株，U87和U251，无论是单层或球体生长的表达的影响。U87细胞自发地形成球状体，并且球状体继续生长，而U251细胞仅在琼脂糖上铺板时形成球状体，并且不以球状体增殖。U87细胞在单层和球状体中对长春碱的耐药性相同，而U251细胞在球状体中的耐药性是单层的4.5倍。荧光长春碱衍生物的分布在细胞的球状体比在单层更不均匀。表达MDR 1的U87细胞在单层中的耐药性增加了9倍，在球状体中增加了50倍，而MDR 1转导的U251细胞使它们在单层中的耐药性增加了20倍，在球状体中增加了160倍。两种细胞系中MDR 1的表达减少了3 H-长春碱和荧光长春碱衍生物的积累。这些结果表明，MDR 1在球状体中比在单层细胞中更有效地赋予耐药性。
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.