RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel
Abstract Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a poor prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been a research focus. Induced ferroptosis of tumour cel...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-85774-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544724019675136 |
|---|---|
| author | Jialin Yuan Cong Liu Chengwei Jiang Ning Liu Zhaoying Yang Hua Xing |
| author_facet | Jialin Yuan Cong Liu Chengwei Jiang Ning Liu Zhaoying Yang Hua Xing |
| author_sort | Jialin Yuan |
| collection | DOAJ |
| description | Abstract Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a poor prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been a research focus. Induced ferroptosis of tumour cells has been proven to increase chemosensitivity, but its ability to sensitize TNBC cells to paclitaxel (PTX) is unknown. In our experiments, measurements of viability and proliferation validated the synergistic effect of PTX combined with RSL3 on TNBC cells. The accumulation of intracellular Fe2+ and lipid reactive oxygen species, as well as the expression of malondialdehyde, illustrated that RSL3 enhanced the chemosensitivity of TNBC to PTX by inducing ferroptosis. Through transcriptome sequencing, a series of differentially expressed genes were identified, in which the expression of cytokines, such as CXCLs, was significantly increased in the treatment group, and the effect of combination therapy on TNBC was enriched mainly in the NFκB signalling pathway. In subsequent validation experiments, the use of the NF-κB inhibitor BAY11-7082 reversed the inhibitory effects of PTX and RSL3 on TNBC cell activity. In a xenograft immunodeficient mouse model, the inhibitory effects of PTX and RSL3 on TNBC in vivo were further verified. Our research validated the synergistic effects of PTX and RSL3 both in vivo and in vitro, with RSL3 inducing ferroptosis by activating the NF-κB signalling pathway, thereby increasing the chemosensitivity of TNBC to PTX. This study provides new insights for improving the therapeutic efficacy of treatment strategies. |
| format | Article |
| id | doaj-art-2b9d7e7a6ad34dfd84b2e667bc4fbed4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2b9d7e7a6ad34dfd84b2e667bc4fbed42025-01-12T12:18:57ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-85774-wRSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxelJialin Yuan0Cong Liu1Chengwei Jiang2Ning Liu3Zhaoying Yang4Hua Xing5Department of Breast Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Breast Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Pathology, China-Japan Union Hospital of Jilin UniversityDepartment of Breast Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Breast Surgery, China-Japan Union Hospital of Jilin UniversityDepartment of Breast Surgery, China-Japan Union Hospital of Jilin UniversityAbstract Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a poor prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been a research focus. Induced ferroptosis of tumour cells has been proven to increase chemosensitivity, but its ability to sensitize TNBC cells to paclitaxel (PTX) is unknown. In our experiments, measurements of viability and proliferation validated the synergistic effect of PTX combined with RSL3 on TNBC cells. The accumulation of intracellular Fe2+ and lipid reactive oxygen species, as well as the expression of malondialdehyde, illustrated that RSL3 enhanced the chemosensitivity of TNBC to PTX by inducing ferroptosis. Through transcriptome sequencing, a series of differentially expressed genes were identified, in which the expression of cytokines, such as CXCLs, was significantly increased in the treatment group, and the effect of combination therapy on TNBC was enriched mainly in the NFκB signalling pathway. In subsequent validation experiments, the use of the NF-κB inhibitor BAY11-7082 reversed the inhibitory effects of PTX and RSL3 on TNBC cell activity. In a xenograft immunodeficient mouse model, the inhibitory effects of PTX and RSL3 on TNBC in vivo were further verified. Our research validated the synergistic effects of PTX and RSL3 both in vivo and in vitro, with RSL3 inducing ferroptosis by activating the NF-κB signalling pathway, thereby increasing the chemosensitivity of TNBC to PTX. This study provides new insights for improving the therapeutic efficacy of treatment strategies.https://doi.org/10.1038/s41598-025-85774-wTriple-negative breast cancerFerroptosisChemosensitivity |
| spellingShingle | Jialin Yuan Cong Liu Chengwei Jiang Ning Liu Zhaoying Yang Hua Xing RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel Scientific Reports Triple-negative breast cancer Ferroptosis Chemosensitivity |
| title | RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel |
| title_full | RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel |
| title_fullStr | RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel |
| title_full_unstemmed | RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel |
| title_short | RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel |
| title_sort | rsl3 induces ferroptosis by activating the nf κb signalling pathway to enhance the chemosensitivity of triple negative breast cancer cells to paclitaxel |
| topic | Triple-negative breast cancer Ferroptosis Chemosensitivity |
| url | https://doi.org/10.1038/s41598-025-85774-w |
| work_keys_str_mv | AT jialinyuan rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel AT congliu rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel AT chengweijiang rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel AT ningliu rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel AT zhaoyingyang rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel AT huaxing rsl3inducesferroptosisbyactivatingthenfkbsignallingpathwaytoenhancethechemosensitivityoftriplenegativebreastcancercellstopaclitaxel |