Combination of AAV-mediated NUPR1 knockdown and trifluoperazine induces premature senescence in human lung adenocarcinoma A549 cells in nude mice
Combination of AAV-mediated NUPR1 knockdown and trifluoperazine induces premature senescence in human lung adenocarcinoma A549 cells in nude mice
复制标题
AAV介导的NUPR1敲低和三氟拉嗪联合诱导裸鼠人肺腺癌A549细胞早衰
DOI：
10.3892/or.2020.7455
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发表时间：
2020-02-01
期刊：
影响因子：
4.2
通讯作者：
Ma, Zhenyi
中科院分区：
文献类型：
--
作者：
Li, Yanzhe;Yin, Yueyuan;Ma, Zhenyi
核蛋白1（NUPR 1）/p8是一种转录调节因子，具有促进肺癌细胞存活的能力。基于腺相关病毒（AAV）的载体是用于基因转移和表达的有效载体。本研究构建了腺相关病毒介导的NUPR 1 shRNA载体，在肺腺癌A549细胞移植瘤模型中有效抑制NUPR 1的表达。三氟拉嗪（TFP）是一种抗精神病药物，能够与NUPR 1结合并模拟癌细胞中的NUPR 1缺陷。还发现TFP和AAV介导的NUPR 1 shRNA递送的组合在携带人肺癌异种移植物的裸鼠中导致显著的肿瘤生长抑制。此外，AAV介导的NUPR 1 shRNA治疗在体外和体内诱导早衰。总的来说，本研究的结果表明AAV-NUPR 1 shRNA和TFP组合在肺癌治疗中的假定作用。
Nuclear protein 1 (NUPR1)/p8, a transcriptional regulator, has the ability to facilitate lung cancer cell survival. Adeno-associated virus (AAV)-based vectors are efficient vehicles for gene transfer and expression. In this study, an AAV-mediated NUPR1 shRNA vector was constructed that effectively inhibited the expression of NUPR1 in a tumor xenograft model derived from lung adenocarcinoma A549 cells. Trifluoperazine (TFP), which is an antipsychotic drug, has the ability to bind to NUPR1 and mimic NUPR1 deficiency in cancer cells. It was also found that the combination of TFP and AAV-mediated NUPR1 shRNA delivery led to significant tumor growth inhibition in nude mice bearing human lung cancer xenografts. Moreover, AAV-mediated NUPR1 shRNA therapy induced premature senescence in vitro and in vivo. Collectively, the findings of this study suggest a putative role for the combination of AAV-NUPR1 shRNA and TFP in lung cancer therapy.