Erlichman C, Wu A
Department of Medical Biophysics, Medicine and Pharmacology, University of Toronto, Ontario, Canada.
Anticancer Res. 1991 Mar-Apr;11(2):671-5.
We determined the cytotoxcity of 5FU alone or with leucovorin in MGH-U1 cells growing as monolayers or spheroids. The 5FU IC50 in spheroid and monolayers was 100 microM in both culture systems. The IC50 of 5FU and 5FU and 100 microM leucovorin in spheroids and monolayers was 100 microM and 50 microM, respectively. [H3]5 FU reached cells at all depths of the spheroid viable rim. Cells isolated from increasing depths of the spheroid viable rim demonstrated increasing resistance to 5FU. 5FU cytotoxicity is increased by leucovorin in monolayer but not spheroids, penetration is not limiting in 5FU cytotoxicity in spheroids and there is increasing resistance to 5FU in the viable rim.
我们测定了单独使用5-氟尿嘧啶（5FU）或与亚叶酸联合使用时，在单层生长或呈球体生长的MGH-U1细胞中的细胞毒性。在两种培养系统中，球体和单层细胞中的5FU半数抑制浓度（IC50）均为100微摩尔。在球体和单层细胞中，5FU与100微摩尔亚叶酸联合使用时的IC50分别为100微摩尔和50微摩尔。[H3]5FU可到达球体存活边缘的所有深度的细胞。从球体存活边缘不同深度分离的细胞对5FU的耐药性逐渐增加。在单层细胞中，亚叶酸可增加5FU的细胞毒性，但在球体中则不然，在球体中渗透不是5FU细胞毒性的限制因素，并且在存活边缘对5FU的耐药性不断增加。
