The role of nuclear factor-kappa B in tamoxifen-resistance of breast cancer
10.3781/j.issn.1000-7431.2018.11.194
- Author:
Xiaohan JIN
1
Author Information
1. Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education
- Publication Type:Journal Article
- Keywords:
Breast neoplasms;
Drug resistance;
Neoplasm;
NF-kappa B;
Tamoxifen
- From:
Tumor
2018;38(7):662-669
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the role of nuclear factor-kappa B (NF-κB) signaling pathway in tamoxifen resistance of breast cancer cells. Methods: MTT assay was used to detect the inhibitory effect of 0-25 μmol/L tamoxifen on the proliferation of hormone recept or-positive breast cancer MCF7 and MCF7R/LCC9 cells. Real-time fluorescence quantitative PCR and Western blotting were used to detect the levels of NF-κB mRNA and its inhibitory subunit α (IKBα) protein in these two breast cancer cells, respectively. MCF7-GC3AI cells were infected with the lentivirus carrying the mutant plasmid pCDH-CMV-IKBα (S32A, S262A), pCDH-CMV-IKKβ (S177E, S181E) and the empty vector pCDH-CMV-Vector. Then the inhibitory effect of tamoxifen in combination with NF-κB signaling pathway inhibitor ACT001 on proliferation of NF-κB signaling pathway-inactivated, -activated and normal MCF7-GC3AI cells was detected by MTT assay. The apoptosis of MCF7-GC3AI cells in each group was observed under a fluorescence microscope, and the clone formation ability of these cells was detected by colony formation assay. Results: MCF7R/LCC9 cells were resistant to tamoxifen as compared with MCF7 cells (P < 0.01). The expression level of negative regulator IKBα of NF-κB signaling pathway in MCF7R/ LCC9 cells was decreased (P < 0.01), and the mRNA level of NF-κB was increased (P < 0.01) as compared with MCF7 cells. After treatment with tamoxifen for 48 h, the proliferation inhibitory ability and apoptosis rate of MCF7-GC3AI-IKKβ cells were decreased (P < 0.01, P < 0.05), and the cell colony formation ability was increased (P < 0.05) as compared with MCF7-GC3AI-Vector cells. But the proliferation inhibitory ability and apoptosis rate of MCF7-GC3AI-IKBα cells were increased (P < 0.05, P < 0.01), and the cell colony formation ability was decreased (P < 0.05) after tamoxifen treatment for 48 h. ACT001, an inhibitor of NF-κB signaling pathway could increase the cytotoxicity of tamoxifen in MCF7R/LCC9 cells (P < 0.01). Conclusion: NF-κB signaling pathway maybe play an important role in the development of tamoxifen resistance in hormone receptor-positive breast cancer cells.
