Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)

Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Repu...

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Autores principales:	Zhao MZ, Li HY, Ma Y, Gong H, Yang S, Fang Q, Hu ZY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Abraxane nano-drug lung cancer drug efficacy molecular mechanisms nanotoxicity Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/26c87ad6820c401f90286d6d79d89501
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spelling	oai:doaj.org-article:26c87ad6820c401f90286d6d79d895012021-12-02T05:39:45ZNanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)1178-2013https://doaj.org/article/26c87ad6820c401f90286d6d79d895012017-03-01T00:00:00Zhttps://www.dovepress.com/nanoparticle-abraxane-possesses-impaired-proliferation-in-a549-cells-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. Keywords: quantitative proteomics, nano-drug, drug efficacy, lung cancer, molecular mechanisms, abraxaneZhao MZLi HYMa YGong HYang SFang QHu ZYDove Medical PressarticleAbraxanenano-druglung cancerdrug efficacymolecular mechanismsnanotoxicityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1685-1697 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Abraxane nano-drug lung cancer drug efficacy molecular mechanisms nanotoxicity Medicine (General) R5-920
spellingShingle	Abraxane nano-drug lung cancer drug efficacy molecular mechanisms nanotoxicity Medicine (General) R5-920 Zhao MZ Li HY Ma Y Gong H Yang S Fang Q Hu ZY Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
description	Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr), a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX). To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1), showed significant differential expression (P<0.05) in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. Keywords: quantitative proteomics, nano-drug, drug efficacy, lung cancer, molecular mechanisms, abraxane
format	article
author	Zhao MZ Li HY Ma Y Gong H Yang S Fang Q Hu ZY
author_facet	Zhao MZ Li HY Ma Y Gong H Yang S Fang Q Hu ZY
author_sort	Zhao MZ
title	Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
title_short	Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
title_full	Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
title_fullStr	Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
title_full_unstemmed	Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)
title_sort	nanoparticle abraxane possesses impaired proliferation in a549 cells due to the underexpression of glucosamine 6-phosphate n-acetyltransferase 1 (gnpnat1/gna1)
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/26c87ad6820c401f90286d6d79d89501
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Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1)

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