Multiple mechanisms of resistance in a series of human testicular teratoma cell lines selected for increasing resistance to etoposide
Multiple mechanisms of resistance in a series of human testicular teratoma cell lines selected for increasing resistance to etoposide
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选择用于增加依托泊苷耐药性的一系列人睾丸畸胎瘤细胞系的多种耐药机制
DOI：
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发表时间：
1994
影响因子：
6.4
通讯作者：
B. Hill
中科院分区：
文献类型：
--
作者：
L. Hosking;R. Whelan;S. Shellard;S. Davies;I. Hickson;M. Danks;B. Hill
在一系列人类睾丸畸胎瘤细胞系（SuSa）的亚系中监测了对VP - 16的抗性机制，这些细胞系分别暴露于分次X射线照射（DXR - 10）或脉冲24小时暴露（VP - 10）或连续暴露条件（VPC2、VPC3和VPC4）下的VP - 16。表达的耐药顺序（根据菌落形成试验得出的icso值从3 - 33倍不等）与临床可能遇到的耐药顺序相当，所有这些耐药亚群对VCR都表现出一定的交叉耐药，并且测试的3种药物选择亚群也证明了对ADR的交叉耐药。抗性与改良的3H‐VP‐16积累无关。然而，在所有耐药亚系中都检测到VP - 16诱导的SSB减少，并且通过线性回归分析发现SSB形成程度与VP - 16抗性之间存在强烈的正相关。通过Western blotting判断，Topo i α蛋白含量仅在连续暴露于VP - 16的亚系中显著降低，但这并不随着抗性表达水平的增加而进展。RNase保护实验也显示，低水平耐药DXR - 10和VP - 10亚系中Topo IIα的表达没有显著差异，而VPC2、VPC3和VPC4亚系中Topo IIα的表达降低了2倍。然而，值得注意的是，在所有药物选择的耐药亚群中，两种交替剪接的Topo i β mRNA水平显著降低（2 - 9倍）。单链构象I多态性分析未检测到Topo Ma一致的ATP结合序列或DNA结合区突变。显著的Pgp过表达仅在最耐药的亚系VPC3和VPC4中被发现，这两个亚系都对VCR表现出4倍的交叉抗性。添加VPM （6.6 μM）可减少3H - VCR积累并部分逆转抗性，这与功能性Pgp在这些亚系中过表达一致。因此，在这一系列序列衍生的VP - 16耐药亚系中，Topo II表达的修饰似乎先于Pgp过表达，并代表了低水平（< 10倍）耐药的主要机制。©1994 Wiley‐Liss, Inc。
Mechanisms of resistance to VP‐16 were monitored in a series of sublines of the human testicular teratoma cell line (SuSa) derived following exposure either to fractionated X‐irradiation (DXR‐10) or to VP‐16 using pulsed 24‐hr exposures (VP 10) or continuous exposure conditions (VPC2, VPC3 and VPC4). Orders of resistance expressed (ranging from 3‐ to 33‐fold based on ICS0 values derived from colony forming assays) were comparable with those likely to be encountered clinically, All of these resistant sublines showed some cross ‐resistance to VCR, and the 3 drug‐selected sublines tested also proved cross‐resistant to ADR. Resistance was not associated with modified 3H‐VP‐16 accumulation. However, decreased VP‐16‐induced SSBs were detectable in all the resistant sublines and a strong positive correlation was noted between the extent of SSB formation and VP‐16 resistance by linear regression analysis. Topo IIα protein content, as judged by Western blotting, was significantly decreased only in the sublines derived by continuous exposure to VP‐16, but this was not progressive with increasing levels of resistance expressed. RNase protection assays also showed no significant differences in Topo IIα expression in the low‐level resistant DXR‐10 and VP 10 sublines, contrasting with the 2‐fold decreases identified in the VPC2, VPC3 and VPC4 sublines. Significantly, however, mRNA levels of two alternately spliced Topo IIβ mRNAs were markedly decreased (2‐ to 9‐fold) in all the drug‐selected resistant sublincs. No mutations in consensus ATP‐binding sequences or in the DNA‐binding region of Topo Ma were detected by single strand conformations I polymorphism analysis. Significant Pgp over express ion was only identified in the most highly resistant sublines VPC3 and VPC4, which both showed 4‐fold cross‐resistance to VCR. Decreased 3H‐VCR accumulation and partial reversal of resistance by VPM (6.6 μM) addition was also identified, consistent with a functional Pgp being overexpressed in these sublines. Modifications of Topo II expression therefore appear to precede Pgp overexpression in this series of sequentially derived VP‐16 resistant sublines and to represent the predominate mechanism underlying low level (< 10‐fold) resistance. © 1994 Wiley‐Liss, Inc.
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获得性耐药人结肠癌细胞系和肺癌细胞系对依托泊苷和替尼泊苷的耐药机制。
影响因子：
11.2
作者：
Long,BH;Wang,L;Lorico,A;Wang,RC;Brattain,MG;Casazza,AM
通讯作者：
Casazza,AM
人类白血病细胞的安吖啶抗性系的表征。
DOI：
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发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Zwelling,LA;Hinds,M;Chan,D;Mayes,J;Sie,KL;Parker,E;Silberman,L;Radcliffe,A;Beran,M;Blick,M
通讯作者：
Blick,M
MCF-7 乳腺肿瘤细胞系中 DNA 的大量损伤与替尼泊苷 (VM-26) 的抗增殖活性之间的分离：诱导基因特异性损伤和基因表达改变的证据。
影响因子：
11.2
作者：
Gewirtz,DA;Orr,MS;Fornari,FA;Randolph,JK;Yalowich,JC;Ritke,MK;Povirk,LF;Bunch,RT
通讯作者：
Bunch,RT
人类肿瘤细胞中 DNA 拓扑异构酶 II 的 M(r) 170,000 同工酶的单链构象多态性分析。
影响因子：
11.2
作者：
Danks,MK;Warmoth,MR;Friche,E;Granzen,B;Bugg,BY;Harker,WG;Zwelling,LA;Futscher,BW;Suttle,DP;Beck,WT
通讯作者：
Beck,WT
与 DNA 拓扑异构酶 II 改变相关的耐药性。
DOI：
10.1016/0065-2571(93)90012-3
发表时间：
1993
期刊：
Advances in enzyme regulation
影响因子：
--
作者：
Beck,WT;Danks,MK;Wolverton,JS;Kim,R;Chen,M
通讯作者：
Chen,M