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Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway

Background: In the present study, we aimed to investigate the effect of proviral integration site for moloney murine leukemia virus-1 (Pim-1) inhibitor (SMI-4a) on the progression of non-small cell lung cancer (NSCLC). Materials and methods: The effects of SMI-4a on proliferation, apoptosis, and cel...

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Autores principales: Jiang, Wenjie, Chen, Yuan, Song, Xing, Shao, Yingjie, Ning, Zhonghua, Gu, Wendong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497832/
https://www.ncbi.nlm.nih.gov/pubmed/31114247
http://dx.doi.org/10.2147/OTT.S203142
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author Jiang, Wenjie
Chen, Yuan
Song, Xing
Shao, Yingjie
Ning, Zhonghua
Gu, Wendong
author_facet Jiang, Wenjie
Chen, Yuan
Song, Xing
Shao, Yingjie
Ning, Zhonghua
Gu, Wendong
author_sort Jiang, Wenjie
collection PubMed
description Background: In the present study, we aimed to investigate the effect of proviral integration site for moloney murine leukemia virus-1 (Pim-1) inhibitor (SMI-4a) on the progression of non-small cell lung cancer (NSCLC). Materials and methods: The effects of SMI-4a on proliferation, apoptosis, and cell cycle of NSCLC cells were examined by in vitro experiments using human NSCLC cell lines (A549 and Ltep-a-2). The pathway regulated by SMI-4a was detected using Western blot. Furthermore, we performed in vivo experiments to assess the effects of SMI-4a on tumor growth using mouse models with NSCLC. Results: Our data demonstrated that SMI-4a could inhibit the proliferation of A549 and Ltep-a-2 cells markedly in a dose-dependent manner (P<0.05). Treatment with 80 μmol/L of SMI-4a for 48 h significantly induced the apoptosis rate of NSCLC cells (P<0.05), and blocked the cell cycle of NSCLC cells in G2/M phase (P<0.05). The phosphorylation levels of PI3K, AKT, and mTOR in NSCLC cells were significantly downregulated by SMI-4a (P<0.05). Result from in vivo experiments demonstrated that SMI-4a could suppress the tumor growth in mouse models with NSCLC (P<0.05). Conclusions: SMI-4a suppresses the progression of NSCLC by blocking the PI3K/AKT/mTOR pathway.
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spelling pubmed-64978322019-05-21 Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway Jiang, Wenjie Chen, Yuan Song, Xing Shao, Yingjie Ning, Zhonghua Gu, Wendong Onco Targets Ther Original Research Background: In the present study, we aimed to investigate the effect of proviral integration site for moloney murine leukemia virus-1 (Pim-1) inhibitor (SMI-4a) on the progression of non-small cell lung cancer (NSCLC). Materials and methods: The effects of SMI-4a on proliferation, apoptosis, and cell cycle of NSCLC cells were examined by in vitro experiments using human NSCLC cell lines (A549 and Ltep-a-2). The pathway regulated by SMI-4a was detected using Western blot. Furthermore, we performed in vivo experiments to assess the effects of SMI-4a on tumor growth using mouse models with NSCLC. Results: Our data demonstrated that SMI-4a could inhibit the proliferation of A549 and Ltep-a-2 cells markedly in a dose-dependent manner (P<0.05). Treatment with 80 μmol/L of SMI-4a for 48 h significantly induced the apoptosis rate of NSCLC cells (P<0.05), and blocked the cell cycle of NSCLC cells in G2/M phase (P<0.05). The phosphorylation levels of PI3K, AKT, and mTOR in NSCLC cells were significantly downregulated by SMI-4a (P<0.05). Result from in vivo experiments demonstrated that SMI-4a could suppress the tumor growth in mouse models with NSCLC (P<0.05). Conclusions: SMI-4a suppresses the progression of NSCLC by blocking the PI3K/AKT/mTOR pathway. Dove 2019-04-23 /pmc/articles/PMC6497832/ /pubmed/31114247 http://dx.doi.org/10.2147/OTT.S203142 Text en © 2019 Jiang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Jiang, Wenjie
Chen, Yuan
Song, Xing
Shao, Yingjie
Ning, Zhonghua
Gu, Wendong
Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title_full Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title_fullStr Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title_full_unstemmed Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title_short Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway
title_sort pim-1 inhibitor smi-4a suppresses tumor growth in non-small cell lung cancer via pi3k/akt/mtor pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497832/
https://www.ncbi.nlm.nih.gov/pubmed/31114247
http://dx.doi.org/10.2147/OTT.S203142
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