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Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma

PURPOSE: Adrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo. METHODS: The expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumo...

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Autores principales: Xu, Lieyu, Qi, Yicheng, Xu, Yunze, Lian, Jianpo, Wang, Xiaojing, Ning, Guang, Wang, Weiqing, Zhu, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094996/
https://www.ncbi.nlm.nih.gov/pubmed/27105537
http://dx.doi.org/10.18632/oncotarget.8827
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author Xu, Lieyu
Qi, Yicheng
Xu, Yunze
Lian, Jianpo
Wang, Xiaojing
Ning, Guang
Wang, Weiqing
Zhu, Yu
author_facet Xu, Lieyu
Qi, Yicheng
Xu, Yunze
Lian, Jianpo
Wang, Xiaojing
Ning, Guang
Wang, Weiqing
Zhu, Yu
author_sort Xu, Lieyu
collection PubMed
description PURPOSE: Adrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo. METHODS: The expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumors by immunohistochemistry. Cell viability of ACC cell lines H295R and SW13 were determined by MTT assay after treatment with the combination of EGFR inhibitor Erlotinib and IGF1R inhibitor NVP-AEW541. Apoptosis was assessed by flow cytometry. The mechanism within intracellular signaling pathways was analyzed by Western blot. Mice bearing human ACC xenografts were treated with Erlotinib and NVP-AEW541, and the effects on tumour growth were assessed. RESULTS: Our results show a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. CONCLUSIONS: In conclusion, coinhibition therapy targeting EGFR and IGF1R may be considerable for treatment of ACC in the future.
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spelling pubmed-50949962016-11-22 Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma Xu, Lieyu Qi, Yicheng Xu, Yunze Lian, Jianpo Wang, Xiaojing Ning, Guang Wang, Weiqing Zhu, Yu Oncotarget Research Paper PURPOSE: Adrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo. METHODS: The expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumors by immunohistochemistry. Cell viability of ACC cell lines H295R and SW13 were determined by MTT assay after treatment with the combination of EGFR inhibitor Erlotinib and IGF1R inhibitor NVP-AEW541. Apoptosis was assessed by flow cytometry. The mechanism within intracellular signaling pathways was analyzed by Western blot. Mice bearing human ACC xenografts were treated with Erlotinib and NVP-AEW541, and the effects on tumour growth were assessed. RESULTS: Our results show a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo. CONCLUSIONS: In conclusion, coinhibition therapy targeting EGFR and IGF1R may be considerable for treatment of ACC in the future. Impact Journals LLC 2016-04-18 /pmc/articles/PMC5094996/ /pubmed/27105537 http://dx.doi.org/10.18632/oncotarget.8827 Text en Copyright: © 2016 Xu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xu, Lieyu
Qi, Yicheng
Xu, Yunze
Lian, Jianpo
Wang, Xiaojing
Ning, Guang
Wang, Weiqing
Zhu, Yu
Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title_full Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title_fullStr Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title_full_unstemmed Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title_short Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma
title_sort co-inhibition of egfr and igf1r synergistically impacts therapeutically on adrenocortical carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094996/
https://www.ncbi.nlm.nih.gov/pubmed/27105537
http://dx.doi.org/10.18632/oncotarget.8827
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