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GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin
BACKGROUND AND OBJECTIVE: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an importan...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542429/ https://www.ncbi.nlm.nih.gov/pubmed/28771580 http://dx.doi.org/10.1371/journal.pone.0182410 |
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author | Gong, Xin Liu, Jing Zhang, Dan Yang, Dawei Min, Zhihui Wen, Xiaoxing Wang, Guifang Li, Huayin Song, Yuanlin Bai, Chunxue Li, Jing Zhou, Jian |
author_facet | Gong, Xin Liu, Jing Zhang, Dan Yang, Dawei Min, Zhihui Wen, Xiaoxing Wang, Guifang Li, Huayin Song, Yuanlin Bai, Chunxue Li, Jing Zhou, Jian |
author_sort | Gong, Xin |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an important role in cell proliferation, migration and apoptosis. However, the expression and function of GLIPR1 in mediating DDP resistance in human lung adenocarcinoma A549/DDP and human large cell lung cancer H460/DDP cells has not yet been reported. METHODS: In this study, real-time PCR (RT-PCR) and western blot were used to examine the mRNA and protein expression of GLIPR1, respectively. Bright-field microscopy, the cell counting kit-8 (CCK-8) assay, flow cytometry analysis and JC-1 dye were used to measure the cellular morphology, proliferation, apoptosis and mitochondrial membrane potential, respectively. RESULTS: Compared to human lung adenocarcinoma A549 cells, the mRNA and protein expression of GLIPR1 were significantly increased in DDP-resistant A549/DDP cells (p < 0.05). Similarly, the mRNA level of GLIPR1 in DDP-resistant H460/DDP cells was also significantly higher than that in DDP-sensitive H460 cells (p < 0.05). Silencing of GLIPR1 in A549/DDP and H460/DDP cells led to increased apoptosis via a mitochondrial signaling pathway following incubation with various concentrations of DDP. Furthermore, GLIPR1 downregulation markedly reduced the protein expression of Bcl-2, and increased the cleaved Poly (ADP-Ribose) Polymerase (PARP) and cleaved caspase-3 in DDP-resistant A549/DDP cells. CONCLUSION: In this study, we demonstrated for the first time that GLIPR1 could modulate the response of DDP-resistant A549/DDP and H460/DDP cells to cisplatin. Therefore, GLIPR1 deserves further investigation in the context of none-small lung cancer (NSCLC). |
format | Online Article Text |
id | pubmed-5542429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55424292017-08-12 GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin Gong, Xin Liu, Jing Zhang, Dan Yang, Dawei Min, Zhihui Wen, Xiaoxing Wang, Guifang Li, Huayin Song, Yuanlin Bai, Chunxue Li, Jing Zhou, Jian PLoS One Research Article BACKGROUND AND OBJECTIVE: Chemotherapy drugs, such as cisplatin (DDP), improve the survival of patients with lung cancer by inducing apoptosis in cancer cells, which quickly develop resistance to DDP through uncharacterized mechanisms. Glioma Pathogenesis-Related Protein 1 (GLIPR1) plays an important role in cell proliferation, migration and apoptosis. However, the expression and function of GLIPR1 in mediating DDP resistance in human lung adenocarcinoma A549/DDP and human large cell lung cancer H460/DDP cells has not yet been reported. METHODS: In this study, real-time PCR (RT-PCR) and western blot were used to examine the mRNA and protein expression of GLIPR1, respectively. Bright-field microscopy, the cell counting kit-8 (CCK-8) assay, flow cytometry analysis and JC-1 dye were used to measure the cellular morphology, proliferation, apoptosis and mitochondrial membrane potential, respectively. RESULTS: Compared to human lung adenocarcinoma A549 cells, the mRNA and protein expression of GLIPR1 were significantly increased in DDP-resistant A549/DDP cells (p < 0.05). Similarly, the mRNA level of GLIPR1 in DDP-resistant H460/DDP cells was also significantly higher than that in DDP-sensitive H460 cells (p < 0.05). Silencing of GLIPR1 in A549/DDP and H460/DDP cells led to increased apoptosis via a mitochondrial signaling pathway following incubation with various concentrations of DDP. Furthermore, GLIPR1 downregulation markedly reduced the protein expression of Bcl-2, and increased the cleaved Poly (ADP-Ribose) Polymerase (PARP) and cleaved caspase-3 in DDP-resistant A549/DDP cells. CONCLUSION: In this study, we demonstrated for the first time that GLIPR1 could modulate the response of DDP-resistant A549/DDP and H460/DDP cells to cisplatin. Therefore, GLIPR1 deserves further investigation in the context of none-small lung cancer (NSCLC). Public Library of Science 2017-08-03 /pmc/articles/PMC5542429/ /pubmed/28771580 http://dx.doi.org/10.1371/journal.pone.0182410 Text en © 2017 Gong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gong, Xin Liu, Jing Zhang, Dan Yang, Dawei Min, Zhihui Wen, Xiaoxing Wang, Guifang Li, Huayin Song, Yuanlin Bai, Chunxue Li, Jing Zhou, Jian GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title | GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title_full | GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title_fullStr | GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title_full_unstemmed | GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title_short | GLIPR1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
title_sort | glipr1 modulates the response of cisplatin-resistant human lung cancer cells to cisplatin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542429/ https://www.ncbi.nlm.nih.gov/pubmed/28771580 http://dx.doi.org/10.1371/journal.pone.0182410 |
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