Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells.
Silencing of mutant p53 by siRNA induces cell cycle arrest and apoptosis in human bladder cancer cells.
复制标题
siRNA 沉默突变体 p53 诱导人膀胱癌细胞的细胞周期停滞和细胞凋亡
DOI：
10.1186/1477-7819-11-22
复制
发表时间：
2013-01-28
影响因子：
3.2
通讯作者：
Xie LP
中科院分区：
文献类型：
--
作者：
Zhu HB;Yang K;Xie YQ;Lin YW;Mao QQ;Xie LP
研究背景p53基因是人类肿瘤中突变频率最高的抑癌基因。据报道，p53突变不仅导致其作为肿瘤抑制因子的能力丧失，而且还导致其获得有助于肿瘤发生的新的癌症相关功能。本研究评价了小干扰RNA沉默突变型p53基因在体外治疗膀胱癌细胞中的作用。方法采用MTT法检测细胞活力，流式细胞术检测细胞周期和凋亡。Western blotting检测相关分子机制。我们还使用MTT法和流式细胞术来研究通过用小干扰（si）RNA敲低突变型p53沉默是否会改变顺铂治疗的敏感性。结果使用以p53突变为特征的人膀胱癌细胞系5637和T24，我们发现通过RNA干扰沉默突变型p53诱导明显的细胞增殖和活力抑制，与诱导G2期细胞周期阻滞和凋亡有关。此外，我们的研究还表明，靶向p53的siRNA协同顺铂在抑制膀胱癌cells.ConclusionsThese研究结果表明，RNA干扰靶向突变型p53可能是一个有前途的治疗策略，用于治疗膀胱癌。
Backgroundp53 is the most frequently mutated tumor-suppressor gene in human cancers. It has been reported that mutations in p53 result not only in the loss of its ability as a tumor suppressor, but also in the gain of novel cancer-related functions that contribute to oncogenesis. The present study evaluated the potential of silencing of mutant p53 by small interfering RNA in the treatment of bladder cancer cellsin vitro.MethodsWe used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability and flow cytometry to detect cell cycle alterations and apoptosis. The related molecular mechanisms were assessed by western blotting. We also used the MTT assay and flow cytometry to investigate if silencing of mutant p53 by knockdown with small interfering (si)RNA would change the sensitivity to cisplatin treatment.ResultsUsing 5637 and T24 human bladder cancer cell lines characterized by mutations in p53, we found that silencing of the mutant p53 by RNA interference induced evident inhibition of cell proliferation and viability, which was related to the induction of G2 phase cell cycle arrest and apoptosis. Moreover, our study also showed that the p53-targeting siRNA cooperated with cisplatin in the inhibition of bladder cancer cells.ConclusionsThese findings suggest that RNA interference targeting mutant p53 may be a promising therapeutic strategy for the treatment of bladder cancer.
登录
查看更多内容
影响因子：
158.5
作者：
Grossman, HB;Natale, RB;Crawford, ED
通讯作者：
Crawford, ED
影响因子：
8
作者：
Blandino, G;Levine, AJ;Oren, M
通讯作者：
Oren, M
影响因子：
64.8
作者：
Castanotto, Daniela;Rossi, John J.
通讯作者：
Rossi, John J.
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
2.6
作者：
Donzelli S;Biagioni F;Fausti F;Strano S;Fontemaggi G;Blandino G
通讯作者：
Blandino G