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The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells

Chemotherapy resistance is the major issue of choriocarcinoma. Apoptosis always is the ultimate outcome of chemotherapeutic drugs, which considered one of the reasons of resistance. We investigated the role of STAT3/NFIL3 signaling‐inhibited apoptosis in chemotherapy resistance and whether Raddeanin...

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Autores principales: Peng, Zheng, Zhang, Chun, Zhou, Wenjun, Wu, Chenchun, Zhang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901038/
https://www.ncbi.nlm.nih.gov/pubmed/29215740
http://dx.doi.org/10.1002/jcp.26362
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author Peng, Zheng
Zhang, Chun
Zhou, Wenjun
Wu, Chenchun
Zhang, Yi
author_facet Peng, Zheng
Zhang, Chun
Zhou, Wenjun
Wu, Chenchun
Zhang, Yi
author_sort Peng, Zheng
collection PubMed
description Chemotherapy resistance is the major issue of choriocarcinoma. Apoptosis always is the ultimate outcome of chemotherapeutic drugs, which considered one of the reasons of resistance. We investigated the role of STAT3/NFIL3 signaling‐inhibited apoptosis in chemotherapy resistance and whether Raddeanin A (RA) could be a new drug to reverse resistance. Established three drug‐resistant cell lines as JEG‐3/MTX, JEG‐3/5‐FU, and JEG‐3/VP16. NFIL3 and STAT3 expression was evaluated in the cells. The IC(50) value, apoptosis rate and apoptins were observed with transfection of siNFIL3, Lenti‐OE™‐NFIL3, shSTAT3, and Lenti‐OE™‐STAT3 or RA treatment. In addition, the luciferase reporter analysis and co‐immunoprecipitation assays were used to investigate the relation of STAT3 and NFIL3. Hyper‐activation of STAT3 and NFIL3 expression were observed in three drug‐resistant cell lines. STAT3 enhanced NFIL3 transcriptional activity by binding the relative promoter region. Activated STAT3/NFIL3 pathway caused low rate of apoptosis which resulted in chemotherapy resistance. RA reduced the resistance index of resistant cells and induced caspase 3 dependent apoptosis, meanwhile it repressed the STAT3/NFIL3 activation. STAT3/NFIL3 axis‐inhibited apoptosis is a novel mechanism of chemotherapy resistance in choriocarcinoma. With the suppression of STAT3/NFIL3 axis and apoptosis induction, RA is a potential agent or lead candidate for improving chemotherapy.
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spelling pubmed-59010382018-04-24 The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells Peng, Zheng Zhang, Chun Zhou, Wenjun Wu, Chenchun Zhang, Yi J Cell Physiol Original Research Articles Chemotherapy resistance is the major issue of choriocarcinoma. Apoptosis always is the ultimate outcome of chemotherapeutic drugs, which considered one of the reasons of resistance. We investigated the role of STAT3/NFIL3 signaling‐inhibited apoptosis in chemotherapy resistance and whether Raddeanin A (RA) could be a new drug to reverse resistance. Established three drug‐resistant cell lines as JEG‐3/MTX, JEG‐3/5‐FU, and JEG‐3/VP16. NFIL3 and STAT3 expression was evaluated in the cells. The IC(50) value, apoptosis rate and apoptins were observed with transfection of siNFIL3, Lenti‐OE™‐NFIL3, shSTAT3, and Lenti‐OE™‐STAT3 or RA treatment. In addition, the luciferase reporter analysis and co‐immunoprecipitation assays were used to investigate the relation of STAT3 and NFIL3. Hyper‐activation of STAT3 and NFIL3 expression were observed in three drug‐resistant cell lines. STAT3 enhanced NFIL3 transcriptional activity by binding the relative promoter region. Activated STAT3/NFIL3 pathway caused low rate of apoptosis which resulted in chemotherapy resistance. RA reduced the resistance index of resistant cells and induced caspase 3 dependent apoptosis, meanwhile it repressed the STAT3/NFIL3 activation. STAT3/NFIL3 axis‐inhibited apoptosis is a novel mechanism of chemotherapy resistance in choriocarcinoma. With the suppression of STAT3/NFIL3 axis and apoptosis induction, RA is a potential agent or lead candidate for improving chemotherapy. John Wiley and Sons Inc. 2018-01-25 2018-07 /pmc/articles/PMC5901038/ /pubmed/29215740 http://dx.doi.org/10.1002/jcp.26362 Text en © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc. This is an open access article under the terms of the http://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 Research Articles
Peng, Zheng
Zhang, Chun
Zhou, Wenjun
Wu, Chenchun
Zhang, Yi
The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title_full The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title_fullStr The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title_full_unstemmed The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title_short The STAT3/NFIL3 signaling axis‐mediated chemotherapy resistance is reversed by Raddeanin A via inducing apoptosis in choriocarcinoma cells
title_sort stat3/nfil3 signaling axis‐mediated chemotherapy resistance is reversed by raddeanin a via inducing apoptosis in choriocarcinoma cells
topic Original Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901038/
https://www.ncbi.nlm.nih.gov/pubmed/29215740
http://dx.doi.org/10.1002/jcp.26362
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