KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling
Triple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype, which has poor prognosis due to the lack of effective targeted drugs. KPT‐330, an inhibitor of the nuclear export protein CRM‐1, has been widely used in clinical medicine. Y219, a novel proteasome inhibitor designed by our...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13588 |
| _version_ | 1827974234154991616 |
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| author | Tiantian Wen Mengzhu Geng Enhe Bai Xueyuan Wang Hang Miao Zhimeng Chen Hui Zhou Jia Wang Jingmiao Shi Yin Zhang Meng Lei Yongqiang Zhu |
| author_facet | Tiantian Wen Mengzhu Geng Enhe Bai Xueyuan Wang Hang Miao Zhimeng Chen Hui Zhou Jia Wang Jingmiao Shi Yin Zhang Meng Lei Yongqiang Zhu |
| author_sort | Tiantian Wen |
| collection | DOAJ |
| description | Triple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype, which has poor prognosis due to the lack of effective targeted drugs. KPT‐330, an inhibitor of the nuclear export protein CRM‐1, has been widely used in clinical medicine. Y219, a novel proteasome inhibitor designed by our group, shows superior efficacy, reduced toxicity, and reduced off‐target effects as compared to the proteasome inhibitor bortezomib. In this study, we investigated the synergistic effect of KPT‐330 and Y219 against TNBC cells, as well as the underlying mechanisms. We report that combination treatment with KPT‐330 and Y219 synergistically inhibited the viability of TNBC cells in vitro and in vivo. Further analysis revealed that the combined use of KPT‐330 and Y219 induced G2‐M phase arrest and apoptosis in TNBC cells, and attenuated nuclear factor kappa B (NF‐κB) signaling by facilitating nuclear localization of IκB‐α. Collectively, these results suggest that the combined use of KPT‐330 and Y219 may be an effective therapeutic strategy for the treatment of TNBC. |
| first_indexed | 2024-04-09T19:51:04Z |
| format | Article |
| id | doaj.art-9b87fd868f754287868a86c5cbcd2ffa |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-09T19:51:04Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-9b87fd868f754287868a86c5cbcd2ffa2023-04-03T06:52:59ZengWileyFEBS Open Bio2211-54632023-04-0113475176210.1002/2211-5463.13588KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signalingTiantian Wen0Mengzhu Geng1Enhe Bai2Xueyuan Wang3Hang Miao4Zhimeng Chen5Hui Zhou6Jia Wang7Jingmiao Shi8Yin Zhang9Meng Lei10Yongqiang Zhu11College of Life Science Nanjing Normal University ChinaCollege of Life Science Nanjing Normal University ChinaCollege of Life Science Nanjing Normal University ChinaCollege of Life Science Nanjing Normal University ChinaCollege of Science Nanjing Forestry University ChinaCollege of Science Nanjing Forestry University ChinaCollege of Life Science Nanjing Normal University ChinaJiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd. Nanjing ChinaJiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd. Nanjing ChinaSchool of Food Science and Pharmaceutical Engineering Nanjing Normal University ChinaCollege of Science Nanjing Forestry University ChinaCollege of Life Science Nanjing Normal University ChinaTriple‐negative breast cancer (TNBC) is an aggressive breast cancer subtype, which has poor prognosis due to the lack of effective targeted drugs. KPT‐330, an inhibitor of the nuclear export protein CRM‐1, has been widely used in clinical medicine. Y219, a novel proteasome inhibitor designed by our group, shows superior efficacy, reduced toxicity, and reduced off‐target effects as compared to the proteasome inhibitor bortezomib. In this study, we investigated the synergistic effect of KPT‐330 and Y219 against TNBC cells, as well as the underlying mechanisms. We report that combination treatment with KPT‐330 and Y219 synergistically inhibited the viability of TNBC cells in vitro and in vivo. Further analysis revealed that the combined use of KPT‐330 and Y219 induced G2‐M phase arrest and apoptosis in TNBC cells, and attenuated nuclear factor kappa B (NF‐κB) signaling by facilitating nuclear localization of IκB‐α. Collectively, these results suggest that the combined use of KPT‐330 and Y219 may be an effective therapeutic strategy for the treatment of TNBC.https://doi.org/10.1002/2211-5463.13588KPT‐330NF‐κBtriple‐negative breast cancerY219 |
| spellingShingle | Tiantian Wen Mengzhu Geng Enhe Bai Xueyuan Wang Hang Miao Zhimeng Chen Hui Zhou Jia Wang Jingmiao Shi Yin Zhang Meng Lei Yongqiang Zhu KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling FEBS Open Bio KPT‐330 NF‐κB triple‐negative breast cancer Y219 |
| title | KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling |
| title_full | KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling |
| title_fullStr | KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling |
| title_full_unstemmed | KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling |
| title_short | KPT‐330 and Y219 exert a synergistic antitumor effect in triple‐negative breast cancer through inhibiting NF‐κB signaling |
| title_sort | kpt 330 and y219 exert a synergistic antitumor effect in triple negative breast cancer through inhibiting nf κb signaling |
| topic | KPT‐330 NF‐κB triple‐negative breast cancer Y219 |
| url | https://doi.org/10.1002/2211-5463.13588 |
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