Iron Oxide Nanoparticles Synergize with Erlotinib to Suppress Refractory Non-Small Cell Lung Cancer Cell Proliferation Through the Inhibition of ErbB/PI3K/AKT and PTEN Activation
Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib, are currently approved for the management of NSCLC. However, primary and acquired resistances to EGFR-TKIs are the major obstacles in the treatment of NSCLC. These resistances have been associated with the development of secondary mutations in EGFR or continued oncogenic signaling despite TKI treatment. In this study, NSCLC cells with wild-type EGFR, A549, H460, H358, H157 which do not respond to EGFR-TKIs, were used. We investigated whether a combination therapy of erlotinib plus iron oxide nanoparticles (IONPs) could sensitize NSCLC cells to erlotinib-induced cancer inhibition. In the 4 NSCLC cells investigated, erlotinib and IONPs combination therapy obviously inhibited NSCLC proliferation in vitro and in vivo, compared with erlotinib treatment alone. This effect was not dependent on erlotinib dose. Activation of ErbB3 was observed in these refractory NSCLC cells. Combined with IONPs, erlotinib could block ErbB3 activity and induce the expression of PTEN, which in turn inhibited the downstream PI3KAKT signaling pathway. These data demonstrate the therapeutic potential of biocompatible IONPs in combination with EGFR-TKIs in NSCLC, thus expanding and repurposing the current therapy for NSCLC.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Journal of biomedical nanotechnology - 13(2017), 4 vom: 05. Apr., Seite 458-68 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Meili [VerfasserIn] |
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| Anmerkungen: |
Date Completed 23.02.2018 Date Revised 23.09.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM280487584 |
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| 245 | 1 | 0 | |a Iron Oxide Nanoparticles Synergize with Erlotinib to Suppress Refractory Non-Small Cell Lung Cancer Cell Proliferation Through the Inhibition of ErbB/PI3K/AKT and PTEN Activation |
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| 500 | |a Date Completed 23.02.2018 | ||
| 500 | |a Date Revised 23.09.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib and gefitinib, are currently approved for the management of NSCLC. However, primary and acquired resistances to EGFR-TKIs are the major obstacles in the treatment of NSCLC. These resistances have been associated with the development of secondary mutations in EGFR or continued oncogenic signaling despite TKI treatment. In this study, NSCLC cells with wild-type EGFR, A549, H460, H358, H157 which do not respond to EGFR-TKIs, were used. We investigated whether a combination therapy of erlotinib plus iron oxide nanoparticles (IONPs) could sensitize NSCLC cells to erlotinib-induced cancer inhibition. In the 4 NSCLC cells investigated, erlotinib and IONPs combination therapy obviously inhibited NSCLC proliferation in vitro and in vivo, compared with erlotinib treatment alone. This effect was not dependent on erlotinib dose. Activation of ErbB3 was observed in these refractory NSCLC cells. Combined with IONPs, erlotinib could block ErbB3 activity and induce the expression of PTEN, which in turn inhibited the downstream PI3KAKT signaling pathway. These data demonstrate the therapeutic potential of biocompatible IONPs in combination with EGFR-TKIs in NSCLC, thus expanding and repurposing the current therapy for NSCLC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a EGFR-TKI | |
| 650 | 4 | |a Iron Oxide Nanoparticles | |
| 650 | 4 | |a Combination Therapy | |
| 650 | 4 | |a ErbB3 | |
| 650 | 4 | |a PI3K/AKT | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
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| 650 | 7 | |a Nanocapsules |2 NLM | |
| 650 | 7 | |a Erlotinib Hydrochloride |2 NLM | |
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| 700 | 1 | |a Sai, Buqing |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Pengfei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Liyang |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Cijun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinye |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guiyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiang, Juanjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Jingqun |e verfasserin |4 aut | |
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