Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis
Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis
复制标题
DOI：
10.1038/nm0196-72
复制
发表时间：
1996-01-01
期刊：
影响因子：
82.9
通讯作者：
Galloway, DA
中科院分区：
文献类型：
--
作者：
Wahl, AF;Donaldson, KL;Galloway, DA
抗癌剂紫杉醇（Taxol（R））稳定微管蛋白聚合，导致有丝分裂停滞和凋亡性细胞死亡。正常人成纤维细胞耗尽功能p53的SV 40 T抗原或HPV-16 E6，和原代胚胎成纤维细胞从p53裸小鼠显示7 - 9倍增加紫杉醇的细胞毒性。p53水平降低与G2/M期阻滞、微核和p53非依赖性紫杉醇诱导的细胞凋亡增加相关。具有完整p53的存活细胞通过有丝分裂进行，并在随后的G1期短暂积累，与p53和p21（cip 1，waf 1）蛋白水平增加一致。这些结果与将p53丢失与对DNA损伤抗癌剂的抗性联系起来的研究相反。
The anticancer agent paclitaxel (Taxol(R)) stabilizes tubulin polymerization resulting in arrest in mitosis and apoptotic cell death. Normal human fibroblasts depleted of functional p53 by SV40 T antigen or HPV-16 E6, and primary embryo fibroblasts from p53 null mice showed seven- to ninefold increased cytotoxicity by paclitaxel. Reduced levels of p53 correlated with increased G2/M phase arrest, micronucleation, and p53-independent paclitaxel-induced apoptosis. Surviving cells with intact p53 progressed through mitosis and transiently accumulated in the subsequent G1 phase, coincident with increased p53 and p21(cip1,waf1) protein levels. These results are in contrast to studies linking p53 loss with resistance to DNA damaging anticancer agents.