PMID- 31922247 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20211112 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 43 IP - 2 DP - 2020 Feb TI - Combination of AAV‑mediated NUPR1 knockdown and trifluoperazine induces premature senescence in human lung adenocarcinoma A549 cells in nude mice. PG - 681-688 LID - 10.3892/or.2020.7455 [doi] AB - 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. FAU - Li, Yanzhe AU - Li Y AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Yin, Yueyuan AU - Yin Y AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Ma, Jinyi AU - Ma J AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Sun, Yanan AU - Sun Y AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Zhou, Ruimin AU - Zhou R AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Cui, Bo AU - Cui B AD - Department of Traditional Chinese Medicine, Yangzhou East Hospital, Yangzhou, Jiangsu 225002, P.R. China. FAU - Zhang, Yuxuan AU - Zhang Y AD - Center for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China. FAU - Yang, Jie AU - Yang J AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Yan, Xiaojie AU - Yan X AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Liu, Zhe AU - Liu Z AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. FAU - Ma, Zhenyi AU - Ma Z AD - Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, P.R. China. LA - eng PT - Journal Article DEP - 20200108 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (NUPR1 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Small Interfering) RN - 214IZI85K3 (Trifluoperazine) SB - IM MH - A549 Cells MH - Adenocarcinoma of Lung/*drug therapy/genetics/pathology MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors/*antagonists & inhibitors/genetics MH - Cell Survival/drug effects MH - Dependovirus/genetics MH - Drug Synergism MH - Gene Knockdown Techniques MH - Genetic Vectors/administration & dosage MH - Humans MH - Lung Neoplasms/drug therapy/*genetics/pathology MH - Mice MH - Mice, Nude MH - Neoplasm Proteins/*antagonists & inhibitors/genetics MH - RNA, Small Interfering/*administration & dosage/pharmacology MH - Trifluoperazine/*administration & dosage/pharmacology MH - Xenograft Model Antitumor Assays OTO - NOTNLM OT - NUPR1/p8 OT - TFP OT - autophagy OT - lung cancer OT - premature senescence EDAT- 2020/01/11 06:00 MHDA- 2020/08/22 06:00 CRDT- 2020/01/11 06:00 PHST- 2019/07/24 00:00 [received] PHST- 2019/12/02 00:00 [accepted] PHST- 2020/01/11 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2020/01/11 06:00 [entrez] AID - 10.3892/or.2020.7455 [doi] PST - ppublish SO - Oncol Rep. 2020 Feb;43(2):681-688. doi: 10.3892/or.2020.7455. Epub 2020 Jan 8.