Cargando…
HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer
Cisplatin resistance is a crucial factor affecting ovarian cancer patient's survival rate, but the primary mechanism underlying cisplatin resistance in ovarian cancer remains unclear, and this prevents the optimal use of cisplatin therapy. Maggot extract (ME) is used in traditional Chinese medi...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169247/ https://www.ncbi.nlm.nih.gov/pubmed/37180757 http://dx.doi.org/10.1155/2023/9335440 |
_version_ | 1785039015183908864 |
---|---|
author | Wang, Daojuan Tang, Xun Ruan, Jianguo Zhu, Zhengquan Wang, Rong Weng, Yajing Zhang, Yaling Wang, Tingyu Huang, Ying Wang, Hongwei Su, Zhenzi Wu, Xiaoke Tao, Gaojian Wang, Yong |
author_facet | Wang, Daojuan Tang, Xun Ruan, Jianguo Zhu, Zhengquan Wang, Rong Weng, Yajing Zhang, Yaling Wang, Tingyu Huang, Ying Wang, Hongwei Su, Zhenzi Wu, Xiaoke Tao, Gaojian Wang, Yong |
author_sort | Wang, Daojuan |
collection | PubMed |
description | Cisplatin resistance is a crucial factor affecting ovarian cancer patient's survival rate, but the primary mechanism underlying cisplatin resistance in ovarian cancer remains unclear, and this prevents the optimal use of cisplatin therapy. Maggot extract (ME) is used in traditional Chinese medicine for patients with comas and patients with gastric cancer when combined with other drug treatments. In this study, we investigated whether ME enhances the sensitivity of ovarian cancer cells to cisplatin. Two ovarian cancer cells—A2780/CDDP and SKOV3/CDDP—were treated with cisplatin and ME in vitro. SKOV3/CDDP cells that stably expressed luciferase were subcutaneously or intraperitoneally injected into BALB/c nude mice to establish a xenograft model, and this was followed by ME/cisplatin treatment. In the presence of cisplatin, ME treatment effectively suppressed the growth and metastasis of cisplatin-resistant ovarian cancer in vivo and in vitro. RNA-sequencing data showed that HSP90AB1 and IGF1R were markedly increased in A2780/CDDP cells. ME treatment markedly decreased the expression of HSP90AB1 and IGF1R, thereby increasing the expression of the proapoptotic proteins p-p53, BAX, and p-H2AX, while the opposite effects were observed for the antiapoptotic protein BCL2. Inhibition of HSP90 ATPase was more beneficial against ovarian cancer in the presence of ME treatment. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in promoting the increased expression of apoptotic proteins and DNA damage response proteins in SKOV3/CDDP cells. Inhibition of cisplatin-induced apoptosis and DNA damage by HSP90AB1 overexpression confers chemoresistance in ovarian cancer. ME can enhance the sensitivity of ovarian cancer cells to cisplatin toxicity by inhibiting HSP90AB1/IGF1R interactions, and this might represent a novel target for overcoming cisplatin resistance in ovarian cancer chemotherapy. |
format | Online Article Text |
id | pubmed-10169247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-101692472023-05-10 HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer Wang, Daojuan Tang, Xun Ruan, Jianguo Zhu, Zhengquan Wang, Rong Weng, Yajing Zhang, Yaling Wang, Tingyu Huang, Ying Wang, Hongwei Su, Zhenzi Wu, Xiaoke Tao, Gaojian Wang, Yong Oxid Med Cell Longev Research Article Cisplatin resistance is a crucial factor affecting ovarian cancer patient's survival rate, but the primary mechanism underlying cisplatin resistance in ovarian cancer remains unclear, and this prevents the optimal use of cisplatin therapy. Maggot extract (ME) is used in traditional Chinese medicine for patients with comas and patients with gastric cancer when combined with other drug treatments. In this study, we investigated whether ME enhances the sensitivity of ovarian cancer cells to cisplatin. Two ovarian cancer cells—A2780/CDDP and SKOV3/CDDP—were treated with cisplatin and ME in vitro. SKOV3/CDDP cells that stably expressed luciferase were subcutaneously or intraperitoneally injected into BALB/c nude mice to establish a xenograft model, and this was followed by ME/cisplatin treatment. In the presence of cisplatin, ME treatment effectively suppressed the growth and metastasis of cisplatin-resistant ovarian cancer in vivo and in vitro. RNA-sequencing data showed that HSP90AB1 and IGF1R were markedly increased in A2780/CDDP cells. ME treatment markedly decreased the expression of HSP90AB1 and IGF1R, thereby increasing the expression of the proapoptotic proteins p-p53, BAX, and p-H2AX, while the opposite effects were observed for the antiapoptotic protein BCL2. Inhibition of HSP90 ATPase was more beneficial against ovarian cancer in the presence of ME treatment. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in promoting the increased expression of apoptotic proteins and DNA damage response proteins in SKOV3/CDDP cells. Inhibition of cisplatin-induced apoptosis and DNA damage by HSP90AB1 overexpression confers chemoresistance in ovarian cancer. ME can enhance the sensitivity of ovarian cancer cells to cisplatin toxicity by inhibiting HSP90AB1/IGF1R interactions, and this might represent a novel target for overcoming cisplatin resistance in ovarian cancer chemotherapy. Hindawi 2023-05-02 /pmc/articles/PMC10169247/ /pubmed/37180757 http://dx.doi.org/10.1155/2023/9335440 Text en Copyright © 2023 Daojuan Wang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wang, Daojuan Tang, Xun Ruan, Jianguo Zhu, Zhengquan Wang, Rong Weng, Yajing Zhang, Yaling Wang, Tingyu Huang, Ying Wang, Hongwei Su, Zhenzi Wu, Xiaoke Tao, Gaojian Wang, Yong HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title | HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title_full | HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title_fullStr | HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title_full_unstemmed | HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title_short | HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer |
title_sort | hsp90ab1 as the druggable target of maggot extract reverses cisplatin resistance in ovarian cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169247/ https://www.ncbi.nlm.nih.gov/pubmed/37180757 http://dx.doi.org/10.1155/2023/9335440 |
work_keys_str_mv | AT wangdaojuan hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT tangxun hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT ruanjianguo hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT zhuzhengquan hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wangrong hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wengyajing hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT zhangyaling hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wangtingyu hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT huangying hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wanghongwei hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT suzhenzi hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wuxiaoke hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT taogaojian hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer AT wangyong hsp90ab1asthedruggabletargetofmaggotextractreversescisplatinresistanceinovariancancer |