Cargando…
CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells
Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a new promising target for the treatment of ovarian cancer. Our previous study showed that cross‐reacting material 197 (CRM197), a specific HB‐EGF inhibitor, significantly reverses resistance against paclitaxel in paclitaxel‐resi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797568/ https://www.ncbi.nlm.nih.gov/pubmed/31490008 http://dx.doi.org/10.1002/cam4.2512 |
_version_ | 1783459856152264704 |
---|---|
author | Tang, Xiao‐han Li, Hui Zheng, Xiu‐shuang Lu, Mei‐song An, Yuan Zhang, Xiao‐lei |
author_facet | Tang, Xiao‐han Li, Hui Zheng, Xiu‐shuang Lu, Mei‐song An, Yuan Zhang, Xiao‐lei |
author_sort | Tang, Xiao‐han |
collection | PubMed |
description | Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a new promising target for the treatment of ovarian cancer. Our previous study showed that cross‐reacting material 197 (CRM197), a specific HB‐EGF inhibitor, significantly reverses resistance against paclitaxel in paclitaxel‐resistant ovarian cancer cells. However, the mechanism of the effect of CRM197 on the reversion of paclitaxel resistance was unclear. In this study, in vitro and in vivo data suggested that CRM197 treatment sensitized paclitaxel‐resistant ovarian cancer cells to paclitaxel, at least in part, via nucleus accumbens‐1 (NAC‐1) and its downstream pathway, DNA damage‐inducible 45‐γ interacting protein (Gadd45gip1)/growth arrest and DNA damage‐inducible 45 (Gadd45), in A2780/Taxol and SKOV3/Taxol cells. The results also showed that CRM197 activated the proapoptotic JNK/p38MAPK pathway to enhance caspase‐3 activity and apoptosis by downregulation of the NAC‐1/Gadd45gip1/Gadd45 pathway, leading to reversion of paclitaxel resistance in A2780/Taxol and SKOV3/Taxol cells. This study provides the first mechanism through which CRM197 significantly reverses resistance against paclitaxel by modulating the NAC‐1/Gadd45gip1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells, and the mechanism of HB‐EGF inhibition as a novel therapeutic strategy for patients with paclitaxel‐resistant ovarian cancer. |
format | Online Article Text |
id | pubmed-6797568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67975682019-10-21 CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells Tang, Xiao‐han Li, Hui Zheng, Xiu‐shuang Lu, Mei‐song An, Yuan Zhang, Xiao‐lei Cancer Med Cancer Prevention Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a new promising target for the treatment of ovarian cancer. Our previous study showed that cross‐reacting material 197 (CRM197), a specific HB‐EGF inhibitor, significantly reverses resistance against paclitaxel in paclitaxel‐resistant ovarian cancer cells. However, the mechanism of the effect of CRM197 on the reversion of paclitaxel resistance was unclear. In this study, in vitro and in vivo data suggested that CRM197 treatment sensitized paclitaxel‐resistant ovarian cancer cells to paclitaxel, at least in part, via nucleus accumbens‐1 (NAC‐1) and its downstream pathway, DNA damage‐inducible 45‐γ interacting protein (Gadd45gip1)/growth arrest and DNA damage‐inducible 45 (Gadd45), in A2780/Taxol and SKOV3/Taxol cells. The results also showed that CRM197 activated the proapoptotic JNK/p38MAPK pathway to enhance caspase‐3 activity and apoptosis by downregulation of the NAC‐1/Gadd45gip1/Gadd45 pathway, leading to reversion of paclitaxel resistance in A2780/Taxol and SKOV3/Taxol cells. This study provides the first mechanism through which CRM197 significantly reverses resistance against paclitaxel by modulating the NAC‐1/Gadd45gip1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells, and the mechanism of HB‐EGF inhibition as a novel therapeutic strategy for patients with paclitaxel‐resistant ovarian cancer. John Wiley and Sons Inc. 2019-09-06 /pmc/articles/PMC6797568/ /pubmed/31490008 http://dx.doi.org/10.1002/cam4.2512 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Prevention Tang, Xiao‐han Li, Hui Zheng, Xiu‐shuang Lu, Mei‐song An, Yuan Zhang, Xiao‐lei CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title | CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title_full | CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title_fullStr | CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title_full_unstemmed | CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title_short | CRM197 reverses paclitaxel resistance by inhibiting the NAC‐1/Gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
title_sort | crm197 reverses paclitaxel resistance by inhibiting the nac‐1/gadd45 pathway in paclitaxel‐resistant ovarian cancer cells |
topic | Cancer Prevention |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797568/ https://www.ncbi.nlm.nih.gov/pubmed/31490008 http://dx.doi.org/10.1002/cam4.2512 |
work_keys_str_mv | AT tangxiaohan crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells AT lihui crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells AT zhengxiushuang crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells AT lumeisong crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells AT anyuan crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells AT zhangxiaolei crm197reversespaclitaxelresistancebyinhibitingthenac1gadd45pathwayinpaclitaxelresistantovariancancercells |