Knockdown of FK506-binding proteins 14 enhances tamoxifen-sensitivity of breast cancer through PI3K/AKT and ERK signaling

Autor: Ma, Yongqiang, Zhao, Mingchuan, Gong, Chengcheng, Miu, Haitao
Rok vydání: 2023
Předmět:
Zdroj: Tropical Journal of Pharmaceutical Research; Vol. 21 No. 11 (2022); 2379-2384
ISSN: 1596-9827
1596-5996
DOI: 10.4314/tjpr.v21i11.16
Popis: Purpose: To investigate the effect of FK506-binding proteins 14 (FKBP14) in the development of chemoresistance of breast cancer. Methods: Breast cancer cell lines (MCF-7 and T47D) were exposed to 4-hydroxytamoxifen over a long period to establish tamoxifen-resistant (TamR) cells. Cell proliferation was evaluated by MTT and colony formation assays, while Transwell assay was used to investigate cell migration and invasion. Results: TamR cells showed resistance to 4-hydroxytamoxifen through increase in IC50 for 4-hydroxytamoxifen in MCF-7 and T47D. The FKBP14 was significantly up-regulated in TamR cells (p < 0.05). Knockdown of FKBP14 reduced the IC50 for 4-hydroxytamoxifen in TamR cells. The number of colony formation in TamR cells was also significantly decreased by silencing of FKBP14 (p < 0.01). Knockdown of FKBP14 inhibited the migration and invasion of TamR cells. Protein expression of p-AKT, p-PI3K and p-ERK in TamR cells were down-regulated by silencing of FKBP14. Conclusion: Loss of FKBP14 enhances sensitivity to tamoxifen in TamR MCF-7 and T47D cells through inactivation of PI3K/AKT and ERK signaling. The role of FKBP14 in tamoxifen-resistant animal models needs further investigation.
Databáze: OpenAIRE