ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231
| Autor: | Bailing Shi, Jingjing Wu, Yuzhu Zhang, Bing Wang, Mei-na Ye, Jiayu Sheng, Hongfeng Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research endocrine system diseases Survival ETS1 IKKα Cell DDP-resistance lcsh:RC254-282 NF-κB Small hairpin RNA 03 medical and health sciences 0302 clinical medicine Genetics medicine Luciferase lcsh:QH573-671 Cisplatin Chemistry lcsh:Cytology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Transplantation 030104 developmental biology medicine.anatomical_structure Oncology Cell culture Apoptosis 030220 oncology & carcinogenesis Cancer research ShRNA Primary Research Chromatin immunoprecipitation medicine.drug |
| Zdroj: | Cancer Cell International, Vol 18, Iss 1, Pp 1-12 (2018) Cancer Cell International |
| ISSN: | 1475-2867 |
| Popis: | Background Platinum-based drugs are used extensively in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC), but their use can be limited by resistance. In this study, we established cisplatin (DDP) resistant TNBC cells to investigate the potential relationship among ETS1, IKKα/NF-κB and resistance. Methods The sensitivity was evaluated by MTT, apoptosis analysis. The intracellular DDP concentration difference was tested by inductively coupled plasma mass spectrometry (ICP-MS) method. Molecular pathological mechanism of DDP resistance was explored by microarray analysis and PPI network analysis. The ETS1, NF-κB signaling change were assessed by western blot and q-PCR in vitro and vivo. The existing binds between ETS1 and the core IKKα promoter were found by luciferase assay and chromatin immunoprecipitation technique (ChIP). Results MDA-MB-231/DDP (231/DDP) cell had a higher IC50 value of cisplatin, lower intracellular DDP concentration, and lower apoptosis ratio than MDA-MB-231 (231/wt) cell line treated with DDP. Increased ABC transporters were induced by the activation of NF-κB pathway in 231/DDP cells. ETS1, RPL6, RBBP8, BIRC2, PIK3A and RARS were six important genes for DDP-resistance based on PPI network and expression validation. Protein expression of ETS1 and IKKα were significantly up-regulated in 231/DDP cells. However, inhibition of ETS1 expression enhances chemo-sensitivity to DDP and reversed the activation of NF-κB pathway in 231/DDP cells and subcutaneous transplantation tumor in vivo. Moreover, there is existing binds between ETS1 and the core IKKα promoter though luciferase assay and ChIP. Conclusion This study enables us to understand the functions of ETS1 in TNBC chemotherapy and suggests that ETS1 could be used as a novel marker of poor response to DDP and a potential therapeutic target for TNBC chemotherapy. |
| Databáze: | OpenAIRE |
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