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p21WAF1/CIP1 基因转录激活可抑制细胞生长并增强肺癌细胞对顺铂的化疗敏感性。

p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell.

机构信息

Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

BMC Cancer. 2010 Nov 19;10:632. doi: 10.1186/1471-2407-10-632.

DOI:10.1186/1471-2407-10-632
PMID:21087528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2995802/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

非小细胞肺癌（NSCLC）预后不良，通常对常规化疗有抗性。细胞周期蛋白依赖性激酶（cdk）抑制剂 p21WAF1/CIP1 的缺失与许多体外细胞模型中的耐药性有关。RNA 激活（RNAa）是一种转录激活现象，由靶向靶基因启动子区域的双链 RNA（dsRNA）指导。

方法

在这项研究中，我们通过将靶向 p21 启动子区域的 dsRNA 转染到 A549 细胞中，探讨了上调 p21 基因表达对 A549 非小细胞肺癌细胞耐药性的影响。

结果

dsRNA 转染后观察到 A549 细胞中 p21 的表达增强，与体外 A549 细胞中 cisplatin 化疗敏感性的显著生长抑制和增强相关。此外，体内实验表明，靶向 p21 启动子区域的 saRNA 可显著抑制 A549 异种移植肿瘤的生长。

结论

这些结果表明 p21 在肺癌耐药过程中发挥作用。此外，本研究还为使用 saRNA 作为上调肺癌中低表达基因的治疗选择提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/a5c2b10395cb/1471-2407-10-632-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/b3464c40f7b9/1471-2407-10-632-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/7229d6c8dbe8/1471-2407-10-632-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/1a84184c0cbd/1471-2407-10-632-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/b2e294368a47/1471-2407-10-632-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/a5c2b10395cb/1471-2407-10-632-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/b3464c40f7b9/1471-2407-10-632-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/7229d6c8dbe8/1471-2407-10-632-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/1a84184c0cbd/1471-2407-10-632-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/b2e294368a47/1471-2407-10-632-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad99/2995802/a5c2b10395cb/1471-2407-10-632-5.jpg

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3
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Int J Biol Sci. 2023 Jun 19;19(10):3159-3183. doi: 10.7150/ijbs.83732. eCollection 2023.
4
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5
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6
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