Co‑expression of murine double minute 2 siRNA and wild‑type p53 induces G1 cell cycle arrest in H1299 cells.
Co‑expression of murine double minute 2 siRNA and wild‑type p53 induces G1 cell cycle arrest in H1299 cells.
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DOI：
10.3892/mmr.2017.7766
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发表时间：
2017-12
影响因子：
3.4
通讯作者：
Long Liu;Ping Zhang;Hua Guo;Xinyu Tang;Lianqin Liu;Jiuling Li;Rui‐Jin Guo;Yangyang Cai;Yanan Liu;Yang Li
中科院分区：
文献类型：
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作者：
Long Liu;Ping Zhang;Hua Guo;Xinyu Tang;Lianqin Liu;Jiuling Li;Rui‐Jin Guo;Yangyang Cai;Yanan Liu;Yang Li
在过去的十年中，晚期非小细胞肺癌的治疗选择有所增加。尽管小分子基因疗法尚未在临床环境中进行测试，但它已成为体外和体内治疗肺癌的有效疗法。特别是，针对p53和小鼠双分钟2 （MDM2）之间的负反馈回路的治疗通过维持肿瘤抑制基因p53的激活提供了有利的结果。本研究在H1299细胞中采用转染的方法，使用小干扰（si）RNA同时敲低MDM2的表达，并过表达野生型p53。MTT法和流式细胞术检测转染对细胞增殖和细胞周期进程的影响，western blotting法和逆转录聚合酶链反应法检测转染对mRNA和蛋白表达的影响。结果表明，与单独抑制MDM2和过表达p53相比，同时抑制MDM2和过表达p53能够抑制H1299细胞的增殖并诱导G1细胞周期阻滞。这些发现表明，si - MDM2 - p53共表达质粒可能诱导细胞周期阻滞，并可能被认为是治疗肺癌的一种新的治疗选择。
The therapeutic options available for the treatment of advanced non-small cell lung cancer have increased over the past decade. Small molecule gene therapy has emerged as an effective therapy for the treatment of lung cancer in vitro and in vivo although it has not been tested in a clinical setting. In particular, therapies that target the negative feedback loop between p53 and murine double minute 2 (MDM2) provide a favorable outcome by maintaining activation of the tumor suppressor gene p53. The present study used transfection to simultaneously knockdown MDM2 expression using small interfering (si)RNA, and overexpress wild‑type p53 in H1299 cells. The effects of transfection on cell proliferation and cell cycle progression were determined using an MTT assay and flow cytometry, and the effects on mRNA and protein expression were determined by western blotting and reverse transcription polymerase chain reaction. The results indicated that simultaneously knocking down MDM2 and overexpressing p53 was able to inhibit proliferation and induce G1 cell cycle arrest in H1299 cells, compared with either alone. These findings indicated that the si‑MDM2‑p53 co‑expression plasmid may induce cell cycle arrest, and may be considered a novel therapeutic option for the treatment of lung cancer.