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Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth
By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribu...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631030/ https://www.ncbi.nlm.nih.gov/pubmed/36104215 http://dx.doi.org/10.1002/advs.202200491 |
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author | Hossen, Md. Nazir Wang, Lin Dwivedi, Shailendra Kumar Dhar Zhang, Yushan Rao, Geeta Elechalwar, Chandra Kumar Sheth, Vinit Dey, Anindya Asfa, Sima Gulla, Suresh Kumar Xu, Chao Fung, Kar‐Ming Robertson, J. David Bieniasz, Magdalena Wilhelm, Stefan Bhattacharya, Resham Mukherjee, Priyabrata |
author_facet | Hossen, Md. Nazir Wang, Lin Dwivedi, Shailendra Kumar Dhar Zhang, Yushan Rao, Geeta Elechalwar, Chandra Kumar Sheth, Vinit Dey, Anindya Asfa, Sima Gulla, Suresh Kumar Xu, Chao Fung, Kar‐Ming Robertson, J. David Bieniasz, Magdalena Wilhelm, Stefan Bhattacharya, Resham Mukherjee, Priyabrata |
author_sort | Hossen, Md. Nazir |
collection | PubMed |
description | By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient‐derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth. Investigating the molecular mechanisms underlying the GNP efficacy reveals that GNPs downregulate insulin growth factor binding protein 2 (IGFBP2) by disrupting its autoregulation via the IGFBP2/mTOR/PTEN axis. This mechanism is validated by treating a cell line‐based human xenograft tumor with GNPs and an mTOR dual‐kinase inhibitor (PI‐103), either individually or in combination with GNPs; GNP and PI‐103 combination therapy inhibit ovarian tumor growth similarly to GNPs alone. This report illustrates how the self‐therapeutic properties of GNPs can be exploited as a discovery tool to identify a critical signaling axis responsible for poor prognosis in ovarian cancer and provides an opportunity to interrogate the axis to improve patient outcomes. |
format | Online Article Text |
id | pubmed-9631030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96310302022-11-07 Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth Hossen, Md. Nazir Wang, Lin Dwivedi, Shailendra Kumar Dhar Zhang, Yushan Rao, Geeta Elechalwar, Chandra Kumar Sheth, Vinit Dey, Anindya Asfa, Sima Gulla, Suresh Kumar Xu, Chao Fung, Kar‐Ming Robertson, J. David Bieniasz, Magdalena Wilhelm, Stefan Bhattacharya, Resham Mukherjee, Priyabrata Adv Sci (Weinh) Research Articles By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient‐derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth. Investigating the molecular mechanisms underlying the GNP efficacy reveals that GNPs downregulate insulin growth factor binding protein 2 (IGFBP2) by disrupting its autoregulation via the IGFBP2/mTOR/PTEN axis. This mechanism is validated by treating a cell line‐based human xenograft tumor with GNPs and an mTOR dual‐kinase inhibitor (PI‐103), either individually or in combination with GNPs; GNP and PI‐103 combination therapy inhibit ovarian tumor growth similarly to GNPs alone. This report illustrates how the self‐therapeutic properties of GNPs can be exploited as a discovery tool to identify a critical signaling axis responsible for poor prognosis in ovarian cancer and provides an opportunity to interrogate the axis to improve patient outcomes. John Wiley and Sons Inc. 2022-09-14 /pmc/articles/PMC9631030/ /pubmed/36104215 http://dx.doi.org/10.1002/advs.202200491 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Hossen, Md. Nazir Wang, Lin Dwivedi, Shailendra Kumar Dhar Zhang, Yushan Rao, Geeta Elechalwar, Chandra Kumar Sheth, Vinit Dey, Anindya Asfa, Sima Gulla, Suresh Kumar Xu, Chao Fung, Kar‐Ming Robertson, J. David Bieniasz, Magdalena Wilhelm, Stefan Bhattacharya, Resham Mukherjee, Priyabrata Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title_full | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title_fullStr | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title_full_unstemmed | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title_short | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
title_sort | gold nanoparticles disrupt the igfbp2/mtor/pten axis to inhibit ovarian cancer growth |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631030/ https://www.ncbi.nlm.nih.gov/pubmed/36104215 http://dx.doi.org/10.1002/advs.202200491 |
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