Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1783314530965651456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5901038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT pengzheng thestat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhangchun thestat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhouwenjun thestat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT wuchenchun thestat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhangyi thestat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT pengzheng stat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhangchun stat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhouwenjun stat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT wuchenchun stat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells AT zhangyi stat3nfil3signalingaxismediatedchemotherapyresistanceisreversedbyraddeaninaviainducingapoptosisinchoriocarcinomacells |