Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Yongqiang Ma¹, Mingchuan Zhao² , Chengcheng Gong², Haitao Miu²

¹Department of Breast Radiotherapy, Cancer Hospital of Chinese Academy of Medical Sciences Shanxi Hospital, Shanxi Cancer Hospital, Taiyuan, Shanxi Province 030013, China; ²Department of Breast Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

For correspondence:- Mingchuan Zhao Email: zhaomingchun87@163.com Tel:+862164175590

Accepted: 28 October 2022 Published: 30 November 2022

Citation: Ma Y, Zhao M, Gong C, Miu H. Knockdown of FK506-binding proteins 14 enhances tamoxifen-sensitivity of breast cancer through PI3K/AKT and ERK signaling. Trop J Pharm Res 2022; 21(11):2379-2384 doi: 10.4314/tjpr.v21i11.16

© 2022 The authors.
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Abstract

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.

Keywords: FKBP14, Tamoxifen-resistant, Breast cancer, Phosphatidylinositol-3-kinase (PI3K)/AKT, extracellular signal-regulated kinase (ERK)