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AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines
BACKGROUND: Small cell lung cancer (SCLC) is a neuroendocrine tumor with poor prognosis. Neuroendocrine tumors possess characteristics of both nerve cells and hormone‐secreting cells; therefore, targeting the neuronal properties of these tumors may lead to the development of new therapeutic options....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons Australia, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569908/ https://www.ncbi.nlm.nih.gov/pubmed/37605807 http://dx.doi.org/10.1111/1759-7714.15075 |
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author | Masumoto, Nami Kato, Shingo Aichi, Masahiro Hasegawa, Sho Sahara, Kota Suyama, Kumiko Sano, Akane Miyazaki, Tomoyuki Okudela, Koji Kaneko, Takeshi Takahashi, Takuya |
author_facet | Masumoto, Nami Kato, Shingo Aichi, Masahiro Hasegawa, Sho Sahara, Kota Suyama, Kumiko Sano, Akane Miyazaki, Tomoyuki Okudela, Koji Kaneko, Takeshi Takahashi, Takuya |
author_sort | Masumoto, Nami |
collection | PubMed |
description | BACKGROUND: Small cell lung cancer (SCLC) is a neuroendocrine tumor with poor prognosis. Neuroendocrine tumors possess characteristics of both nerve cells and hormone‐secreting cells; therefore, targeting the neuronal properties of these tumors may lead to the development of new therapeutic options. Among the endogenous signaling pathways in the nervous system, targeting the glutamate pathway may be a useful strategy for glioblastoma treatment. Perampanel, an antagonist of the synaptic glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor (AMPAR), has been reported to be effective in patients with glioblastoma. In this study, we aimed to investigate the antitumor effects of AMPAR antagonists in human SCLC cell lines. METHODS: We performed to examine the expression of AMPAR using Western blot and immunohistochemical analysis. The antitumor effects of AMPAR antagonists on human SCLC cell lines were investigated in vitro and in vivo. We also analyzed the signaling pathway of AMPAR antagonists in SCLC cell lines. Statistical analysis was performed by the GraphPad Prism 6 software. RESULTS: We first examined the expression of endogenous AMPAR in six human SCLC cell lines, detecting AMPAR proteins in all of them. Next, we tested the anti−proliferative effect of two AMPAR antagonists, talampanel and cyanquixaline, using SCLC cells in vitro and in vivo. Both AMPAR antagonists inhibited cell proliferation and mitogen‐activated protein kinase (MAPK) phosphorylation in SCLC cells in vitro. Further, we observed reduced proliferation of implanted cell lines in an in vivo setting, assessed by Ki‐67 immunohistochemistry. Additionally, using immunohistochemical analysis we confirmed AMPAR protein expression in human SCLC samples. CONCLUSION: AMPAR may be a potential therapeutic target for SCLC. |
format | Online Article Text |
id | pubmed-10569908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley & Sons Australia, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-105699082023-10-13 AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines Masumoto, Nami Kato, Shingo Aichi, Masahiro Hasegawa, Sho Sahara, Kota Suyama, Kumiko Sano, Akane Miyazaki, Tomoyuki Okudela, Koji Kaneko, Takeshi Takahashi, Takuya Thorac Cancer Original Articles BACKGROUND: Small cell lung cancer (SCLC) is a neuroendocrine tumor with poor prognosis. Neuroendocrine tumors possess characteristics of both nerve cells and hormone‐secreting cells; therefore, targeting the neuronal properties of these tumors may lead to the development of new therapeutic options. Among the endogenous signaling pathways in the nervous system, targeting the glutamate pathway may be a useful strategy for glioblastoma treatment. Perampanel, an antagonist of the synaptic glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor (AMPAR), has been reported to be effective in patients with glioblastoma. In this study, we aimed to investigate the antitumor effects of AMPAR antagonists in human SCLC cell lines. METHODS: We performed to examine the expression of AMPAR using Western blot and immunohistochemical analysis. The antitumor effects of AMPAR antagonists on human SCLC cell lines were investigated in vitro and in vivo. We also analyzed the signaling pathway of AMPAR antagonists in SCLC cell lines. Statistical analysis was performed by the GraphPad Prism 6 software. RESULTS: We first examined the expression of endogenous AMPAR in six human SCLC cell lines, detecting AMPAR proteins in all of them. Next, we tested the anti−proliferative effect of two AMPAR antagonists, talampanel and cyanquixaline, using SCLC cells in vitro and in vivo. Both AMPAR antagonists inhibited cell proliferation and mitogen‐activated protein kinase (MAPK) phosphorylation in SCLC cells in vitro. Further, we observed reduced proliferation of implanted cell lines in an in vivo setting, assessed by Ki‐67 immunohistochemistry. Additionally, using immunohistochemical analysis we confirmed AMPAR protein expression in human SCLC samples. CONCLUSION: AMPAR may be a potential therapeutic target for SCLC. John Wiley & Sons Australia, Ltd 2023-08-22 /pmc/articles/PMC10569908/ /pubmed/37605807 http://dx.doi.org/10.1111/1759-7714.15075 Text en © 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Masumoto, Nami Kato, Shingo Aichi, Masahiro Hasegawa, Sho Sahara, Kota Suyama, Kumiko Sano, Akane Miyazaki, Tomoyuki Okudela, Koji Kaneko, Takeshi Takahashi, Takuya AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title |
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title_full |
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title_fullStr |
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title_full_unstemmed |
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title_short |
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
title_sort | ampar receptor inhibitors suppress proliferation of human small cell lung cancer cell lines |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10569908/ https://www.ncbi.nlm.nih.gov/pubmed/37605807 http://dx.doi.org/10.1111/1759-7714.15075 |
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