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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...

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Autores principales: Gong, Xin, Liu, Jing, Zhang, Dan, Yang, Dawei, Min, Zhihui, Wen, Xiaoxing, Wang, Guifang, Li, Huayin, Song, Yuanlin, Bai, Chunxue, Li, Jing, Zhou, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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).
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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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