BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis
文献类型：期刊论文
| 作者 | Li, Guang1,2; Zheng, Yan-Hua2; Xu, Li2; Feng, Juan2; Tang, Hai-Long2; Luo, Cheng3 ; Song, Yan-Ping1; Chen, Xie-Qun2
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| 刊名 | THERAPEUTIC ADVANCES IN HEMATOLOGY
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| 出版日期 | 2020-06-01 |
| 卷号 | 11页码:12 |
| 关键词 | apoptosis BRD4 inhibitor G1 phase cell cycle checkpoint multiple myeloma |
| ISSN号 | 2040-6207 |
| DOI | 10.1177/2040620720932686 |
| 通讯作者 | Chen, Xie-Qun(xiequnchen1@163.com) |
| 英文摘要 | Background: Multiple myeloma (MM) is the second most common hematological neoplasm. Wide administration of bortezomib significantly improves the survival of MM patients compared with conventional chemotherapy. Bromodomain-containing protein 4 (BRD4) inhibitors also have been demonstrated to retard cell proliferation and induce cellular apoptosis in various cancers. However, it is unclear whether the BRD4 inhibitor nitroxoline plus bortezomib has a synergistic anti-tumor effect on MM. Methods: Cell viability was determined via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and cell apoptosis were assessed via flow cytometry. Protein expression levels were determined via western blotting. The expression of apoptosis-related proteins in xenograft tissue were detected by means of immunohistochemistry. Results: Treatment with nitroxoline or bortezomib suppressed cell proliferation, and caused G0/G1 phase arrest and apoptosis in H929 and RPMI8226 cells. Furthermore, nitroxoline intensified the retardation of cell proliferation, as well as further enhanced the G0/G1 phase arrest and apoptosis induced by bortezomib in H929 and RPMI8226 cells. The western blot analysis revealed that nitroxoline or bortezomib treatment markedly diminished the levels of Bcl-2 and cyclin D1, and increased the levels of p21, Bax, cleaved PARP and cleaved caspase-3. Combination of these two agents was observed to result in further marked changes on these levels compared with nitroxoline or bortezomib treatment alone. What is more, in the xenograft tumor model, combinative treatment markedly inhibited tumor growth compared with the single drug treatment. Conclusion: Combination of bortezomib with nitroxoline has a synergistic anti-tumor activity in MM cells and may be a novel treatment method for MM. |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; OVARIAN-CANCER CELLS ; ARREST ; AUTOPHAGY |
| 资助项目 | National Natural Science Foundation of China[81172247] ; Natural Science Foundation of Shaanxi Province[2017JM8025] |
| WOS研究方向 | Hematology |
| 语种 | 英语 |
| WOS记录号 | WOS:000540784200001 |
| 出版者 | SAGE PUBLICATIONS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291701]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Xie-Qun |
| 作者单位 | 1.Xian Cent Hosp, Inst Hematol, 161 Xiwu Rd, Xian 710003, Shaanxi, Peoples R China 2.Fourth Mil Med Univ, Dept Hematol, Xijing Hosp, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China 3.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Guang,Zheng, Yan-Hua,Xu, Li,et al. BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis[J]. THERAPEUTIC ADVANCES IN HEMATOLOGY,2020,11:12. |
| APA | Li, Guang.,Zheng, Yan-Hua.,Xu, Li.,Feng, Juan.,Tang, Hai-Long.,...&Chen, Xie-Qun.(2020).BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis.THERAPEUTIC ADVANCES IN HEMATOLOGY,11,12. |
| MLA | Li, Guang,et al."BRD4 inhibitor nitroxoline enhances the sensitivity of multiple myeloma cells to bortezomib in vitro and in vivo by promoting mitochondrial pathway-mediated cell apoptosis".THERAPEUTIC ADVANCES IN HEMATOLOGY 11(2020):12. |
入库方式： OAI收割
来源：上海药物研究所
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