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Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway

BACKGROUND: Reducing drug resistance in tumor cells has become an important issue for cancer treatment. The purpose of this study was to investigate whether IL-22 was involved in lung cancer cell resistance to paclitaxel (PTX), and to explore the underlying molecular mechanism. MATERIAL/METHODS: Non...

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Autores principales: Li, Chenchen, Zhao, Xia, Yang, Yang, Liu, Siwen, Liu, Yun, Li, Xiaoyou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952719/
https://www.ncbi.nlm.nih.gov/pubmed/29723165
http://dx.doi.org/10.12659/MSM.907336
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author Li, Chenchen
Zhao, Xia
Yang, Yang
Liu, Siwen
Liu, Yun
Li, Xiaoyou
author_facet Li, Chenchen
Zhao, Xia
Yang, Yang
Liu, Siwen
Liu, Yun
Li, Xiaoyou
author_sort Li, Chenchen
collection PubMed
description BACKGROUND: Reducing drug resistance in tumor cells has become an important issue for cancer treatment. The purpose of this study was to investigate whether IL-22 was involved in lung cancer cell resistance to paclitaxel (PTX), and to explore the underlying molecular mechanism. MATERIAL/METHODS: Non-small cell lung cancer (NSCLC) cell line A549 and the drug resistant cell line A549/PTX were used in the present study. The inhibitory rate of PTX on A549 and A549/PTX cell proliferation was determined by MTT assay and the half-maximal inhibitory concentration (IC(50)) value was calculated. The expression level of IL-22 was detected using Western blot and qRT-PCR. To elucidate the mechanism by which IL-22 is involved in PTX resistance, a stable IL-22-silenced A549/PTX cell line was generated by using IL-22-siRNA. Cell apoptosis was analyzed by flow cytometry, and the c-Jun N-terminal kinase (JNK) signal pathway was determined using Western blot analysis. RESULTS: We found that IL-22 expression level was markedly higher in A549/PTX cells than in A549 cells, and IL-22 gene knockdown significantly enhanced the cell proliferation inhibition rate of PTX to A549/PTX cells and decreased the IC(50) value of PTX to A549/PTX cells, indicating IL-22 was involved in cell PTX resistance. Our findings also suggest that IL-22 knockdown notably increased PTX induced apoptosis in A549/PTX cells. Moreover, the results showed that p-JNK and Caspase 3 expression were significantly increased in IL-22 knockdown A549/PTX cells, while Bcl-2 expression was significantly decreased. CONCLUSIONS: IL-22 is involved in A549 cell resistance to PTX through regulating cell apoptosis via the JNK signaling pathway.
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spelling pubmed-59527192018-05-17 Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway Li, Chenchen Zhao, Xia Yang, Yang Liu, Siwen Liu, Yun Li, Xiaoyou Med Sci Monit Lab/In Vitro Research BACKGROUND: Reducing drug resistance in tumor cells has become an important issue for cancer treatment. The purpose of this study was to investigate whether IL-22 was involved in lung cancer cell resistance to paclitaxel (PTX), and to explore the underlying molecular mechanism. MATERIAL/METHODS: Non-small cell lung cancer (NSCLC) cell line A549 and the drug resistant cell line A549/PTX were used in the present study. The inhibitory rate of PTX on A549 and A549/PTX cell proliferation was determined by MTT assay and the half-maximal inhibitory concentration (IC(50)) value was calculated. The expression level of IL-22 was detected using Western blot and qRT-PCR. To elucidate the mechanism by which IL-22 is involved in PTX resistance, a stable IL-22-silenced A549/PTX cell line was generated by using IL-22-siRNA. Cell apoptosis was analyzed by flow cytometry, and the c-Jun N-terminal kinase (JNK) signal pathway was determined using Western blot analysis. RESULTS: We found that IL-22 expression level was markedly higher in A549/PTX cells than in A549 cells, and IL-22 gene knockdown significantly enhanced the cell proliferation inhibition rate of PTX to A549/PTX cells and decreased the IC(50) value of PTX to A549/PTX cells, indicating IL-22 was involved in cell PTX resistance. Our findings also suggest that IL-22 knockdown notably increased PTX induced apoptosis in A549/PTX cells. Moreover, the results showed that p-JNK and Caspase 3 expression were significantly increased in IL-22 knockdown A549/PTX cells, while Bcl-2 expression was significantly decreased. CONCLUSIONS: IL-22 is involved in A549 cell resistance to PTX through regulating cell apoptosis via the JNK signaling pathway. International Scientific Literature, Inc. 2018-05-03 /pmc/articles/PMC5952719/ /pubmed/29723165 http://dx.doi.org/10.12659/MSM.907336 Text en © Med Sci Monit, 2018 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Lab/In Vitro Research
Li, Chenchen
Zhao, Xia
Yang, Yang
Liu, Siwen
Liu, Yun
Li, Xiaoyou
Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title_full Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title_fullStr Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title_full_unstemmed Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title_short Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway
title_sort interleukin-22 (il-22) regulates apoptosis of paclitaxel-resistant non-small cell lung cancer cells through c-jun n-terminal kinase signaling pathway
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952719/
https://www.ncbi.nlm.nih.gov/pubmed/29723165
http://dx.doi.org/10.12659/MSM.907336
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