AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines
Abstract 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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-10-01
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| Series: | Thoracic Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/1759-7714.15075 |
| _version_ | 1827794563777953792 |
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| author | Nami Masumoto Shingo Kato Masahiro Aichi Sho Hasegawa Kota Sahara Kumiko Suyama Akane Sano Tomoyuki Miyazaki Koji Okudela Takeshi Kaneko Takuya Takahashi |
| author_facet | Nami Masumoto Shingo Kato Masahiro Aichi Sho Hasegawa Kota Sahara Kumiko Suyama Akane Sano Tomoyuki Miyazaki Koji Okudela Takeshi Kaneko Takuya Takahashi |
| author_sort | Nami Masumoto |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T18:35:42Z |
| format | Article |
| id | doaj.art-418c4c541dbf4c5191c29bc5273bfa0b |
| institution | Directory Open Access Journal |
| issn | 1759-7706 1759-7714 |
| language | English |
| last_indexed | 2024-03-11T18:35:42Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Thoracic Cancer |
| spelling | doaj.art-418c4c541dbf4c5191c29bc5273bfa0b2023-10-12T23:31:23ZengWileyThoracic Cancer1759-77061759-77142023-10-0114292897290810.1111/1759-7714.15075AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell linesNami Masumoto0Shingo Kato1Masahiro Aichi2Sho Hasegawa3Kota Sahara4Kumiko Suyama5Akane Sano6Tomoyuki Miyazaki7Koji Okudela8Takeshi Kaneko9Takuya Takahashi10Department of Pulmonology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Clinical Cancer Genomics Yokohama City University Hospital Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Gastroenterology and Hepatology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Pathology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Pulmonology Yokohama City University Graduate School of Medicine Yokohama JapanDepartment of Physiology Yokohama City University Graduate School of Medicine Yokohama JapanAbstract 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.https://doi.org/10.1111/1759-7714.15075AMPARcyanquixalinesmall cell lung cancertalampanelα‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor |
| spellingShingle | Nami Masumoto Shingo Kato Masahiro Aichi Sho Hasegawa Kota Sahara Kumiko Suyama Akane Sano Tomoyuki Miyazaki Koji Okudela Takeshi Kaneko Takuya Takahashi AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines Thoracic Cancer AMPAR cyanquixaline small cell lung cancer talampanel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor |
| 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 | AMPAR cyanquixaline small cell lung cancer talampanel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor |
| url | https://doi.org/10.1111/1759-7714.15075 |
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