HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer
Objective: Hepatitis B X-interacting protein (HBXIP) plays an important role in breast tumorigenesis, tumor growth and metastasis, but its functional contribution in radioresistance remains poorly understood. As radiotherapy served as an essential adjuvant treatment, uncovering the role of HBXIP as...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-06-01
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| Series: | Radiation Medicine and Protection |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266655572100023X |
| _version_ | 1827829443903619072 |
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| author | Xiaofei Chu Wang Zheng Qianping Chen Chen Wang Saijun Fan Chunlin Shao |
| author_facet | Xiaofei Chu Wang Zheng Qianping Chen Chen Wang Saijun Fan Chunlin Shao |
| author_sort | Xiaofei Chu |
| collection | DOAJ |
| description | Objective: Hepatitis B X-interacting protein (HBXIP) plays an important role in breast tumorigenesis, tumor growth and metastasis, but its functional contribution in radioresistance remains poorly understood. As radiotherapy served as an essential adjuvant treatment, uncovering the role of HBXIP as well as its downstream molecular XIAP in radioresistance could benefit for the development of individual therapy strategy. Methods: Immunohistochemistry of 42 breast cancer tissue samples and Western blot analysis of proteins from MCF-7 and MDA-MB-231 cells exposed to fractioned doses (γ-rays) were used to identify the expression of HBXIP/XIAP in breast cancer. To verify the radioresistance effects and potential mechanism, the cells were treated with designed pCMV and siRNA of targeting genes, and then measured with MTT assay, clonogenic survival assay and flow cytometry. Furthermore, a subcutaneous xenotransplanted tumor model of breast cancer was established in nude mice to validate the radioresistization effect of HBXIP in vivo. Results: HBXIP and XIAP expression levels in breast cancer tissues were positively correlated with chemo-radiotherapy resistance of breast cancer. Overexpression of HBXIP could desensitize MCF-7 and MDA-MB-231 cells to irradiation by inhibiting radiation-induced cell apoptosis, and knockdown of HBXIP in these cells had the converse response. Moreover, up-regulation of HBXIP resulted in the increase of XIAP and NF-κB levels in vitro and in vivo, while down-regulation of HBXIP led to the opposite effects. In addition, inhibition of XIAP and NF-κB abrogated the HBXIP overexpression induced radioresistization and increased cell apoptosis (25.8% augment for siRNA XIAP and 28.1% for NF-κB in MDA-MB-231 cells; 25.4% augment for siRNA XIAP and 27.2% for NF–κB in MCF-7 cells). Conclusions: HBXIP enhances radioresistance of human breast cancer cells via upregulating XIAP, and targeting the HBXIP–NF–κB-XIAP pathway may be a potentially effective strategy to enhance the efficacy of radiotherapy for human breast cancer. |
| first_indexed | 2024-03-12T04:04:14Z |
| format | Article |
| id | doaj.art-0f2ebefb07ec445c879a70e13604ac79 |
| institution | Directory Open Access Journal |
| issn | 2666-5557 |
| language | English |
| last_indexed | 2024-03-12T04:04:14Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Radiation Medicine and Protection |
| spelling | doaj.art-0f2ebefb07ec445c879a70e13604ac792023-09-03T11:22:48ZengElsevierRadiation Medicine and Protection2666-55572021-06-01223947HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancerXiaofei Chu0Wang Zheng1Qianping Chen2Chen Wang3Saijun Fan4Chunlin Shao5Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2904 Xietu Road, Shanghai, 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2904 Xietu Road, Shanghai, 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2904 Xietu Road, Shanghai, 200032, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2904 Xietu Road, Shanghai, 200032, ChinaTianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 238 Baidi Road, Tianjin, 300192, China; Corresponding author.Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No. 2904 Xietu Road, Shanghai, 200032, China; Corresponding author.Objective: Hepatitis B X-interacting protein (HBXIP) plays an important role in breast tumorigenesis, tumor growth and metastasis, but its functional contribution in radioresistance remains poorly understood. As radiotherapy served as an essential adjuvant treatment, uncovering the role of HBXIP as well as its downstream molecular XIAP in radioresistance could benefit for the development of individual therapy strategy. Methods: Immunohistochemistry of 42 breast cancer tissue samples and Western blot analysis of proteins from MCF-7 and MDA-MB-231 cells exposed to fractioned doses (γ-rays) were used to identify the expression of HBXIP/XIAP in breast cancer. To verify the radioresistance effects and potential mechanism, the cells were treated with designed pCMV and siRNA of targeting genes, and then measured with MTT assay, clonogenic survival assay and flow cytometry. Furthermore, a subcutaneous xenotransplanted tumor model of breast cancer was established in nude mice to validate the radioresistization effect of HBXIP in vivo. Results: HBXIP and XIAP expression levels in breast cancer tissues were positively correlated with chemo-radiotherapy resistance of breast cancer. Overexpression of HBXIP could desensitize MCF-7 and MDA-MB-231 cells to irradiation by inhibiting radiation-induced cell apoptosis, and knockdown of HBXIP in these cells had the converse response. Moreover, up-regulation of HBXIP resulted in the increase of XIAP and NF-κB levels in vitro and in vivo, while down-regulation of HBXIP led to the opposite effects. In addition, inhibition of XIAP and NF-κB abrogated the HBXIP overexpression induced radioresistization and increased cell apoptosis (25.8% augment for siRNA XIAP and 28.1% for NF-κB in MDA-MB-231 cells; 25.4% augment for siRNA XIAP and 27.2% for NF–κB in MCF-7 cells). Conclusions: HBXIP enhances radioresistance of human breast cancer cells via upregulating XIAP, and targeting the HBXIP–NF–κB-XIAP pathway may be a potentially effective strategy to enhance the efficacy of radiotherapy for human breast cancer.http://www.sciencedirect.com/science/article/pii/S266655572100023XHBXIPXIAPRadioresistanceBreast cancer |
| spellingShingle | Xiaofei Chu Wang Zheng Qianping Chen Chen Wang Saijun Fan Chunlin Shao HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer Radiation Medicine and Protection HBXIP XIAP Radioresistance Breast cancer |
| title | HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer |
| title_full | HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer |
| title_fullStr | HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer |
| title_full_unstemmed | HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer |
| title_short | HBXIP contributes to radioresistance through NF-κB-mediated expression of XIAP in breast cancer |
| title_sort | hbxip contributes to radioresistance through nf κb mediated expression of xiap in breast cancer |
| topic | HBXIP XIAP Radioresistance Breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S266655572100023X |
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