p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell.
p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell.
复制标题
p21WAF1/CIP1基因转录激活可抑制肺癌细胞的生长并增强对顺铂的化疗敏感性。
DOI：
10.1186/1471-2407-10-632
复制
发表时间：
2010-11-19
期刊：
影响因子：
3.8
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Wei J;Zhao J;Long M;Han Y;Wang X;Lin F;Ren J;He T;Zhang H
非小细胞肺癌（NSCLC）预后差，通常对常规化疗耐药。在许多体外细胞模型中，p21 WAF 1/CIP 1（一种细胞周期蛋白依赖性激酶（cdk）抑制剂）的缺失与耐药性有关。RNA激活（RNAa）是双链RNA（dsRNA）靶向靶基因启动子区的转录激活现象。本研究通过转染靶向p21启动子区的双链RNA，探讨p21基因表达上调对A549细胞耐药性的影响。转染dsRNA后，A549细胞p21表达增强，这与A549细胞体外生长抑制和顺铂化疗敏感性增强有关。此外，体内实验表明，靶向p21启动子区域的saRNA可以显著抑制A549异种移植瘤的生长。这些结果表明，p21在肺癌耐药过程中起作用。此外，这项研究还为使用saRNA作为上调肺癌低表达基因的治疗选择提供了证据。
Non-small-cell lung carcinomas (NSCLCs) exhibit poor prognosis and are usually resistant to conventional chemotherapy. Absence of p21WAF1/CIP1, a cyclin-dependent kinase (cdk) inhibitor, has been linked to drug resistance in many in vitro cellular models. RNA activation (RNAa) is a transcriptional activation phenomena guided by double-strand RNA (dsRNA) targeting promoter region of target gene. In this study, we explored the effect of up-regulation of p21 gene expression on drug-resistance in A549 non-small-cell lung carcinoma cells by transfecting the dsRNA targeting the promoter region of p21 into A549 cells. Enhanced p21 expression was observed in A549 cells after transfection of dsRNA, which was correlated with a significant growth inhibition and enhancement of chemosensitivity to cisplatin in A549 cells in vitro. Moreover, in vivo experiment showed that saRNA targeting the promoter region of p21 could significantly inhibit A549 xenograft tumor growth. These results indicate that p21 plays a role in lung cancer drug-resistance process. In addition, this study also provides evidence for the usage of saRNA as a therapeutic option for up-regulating lower-expression genes in lung cancer.
登录
查看更多内容
影响因子：
64.8
作者：
Waldman, T;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
8
作者：
Medema, RH;Klompmaker, R;Rijksen, G
通讯作者：
Rijksen, G
影响因子：
5.3
作者：
Niculescu, AB;Chen, XB;Reed, SI
通讯作者：
Reed, SI
影响因子：
5.3
作者：
Ogryzko, VV;Wong, P;Howard, BH
通讯作者：
Howard, BH
saRNA上调p21WAF1/Cip1诱导T24人膀胱癌细胞G1期阻滞和细胞凋亡
影响因子：
9.7
作者：
Yang, Kai;Zheng, Xiang-Yi;Xie, Li-Ping
通讯作者：
Xie, Li-Ping