title: Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1).
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.
authors.affiliation: 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.
authors.forename: Minzhi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Gong
authors.affiliation: 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.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: 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.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000072283:A549 Cells; D000199:Actins / Q000378:metabolism; D000068196:Albumin-Bound Paclitaxel / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D051081:Glucosamine 6-Phosphate N-Acetyltransferase / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000473:pathology*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology; D058105:Polymerization; D040901:Proteomics; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D000199:Actins; D000068196:Albumin-Bound Paclitaxel; D051081:Glucosamine 6-Phosphate N-Acetyltransferase; D017239:Paclitaxel
keywords: abraxane; drug efficacy; lung cancer; molecular mechanisms; nano-drug; quantitative proteomics