Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4

Pei Zhang; Nan Wu; Zhi-Jun Song; Zheng-Fu Tai

doi:10.1155/2022/6730559

Paeoniflorin Enhances the Sensitivity of ER-Positive Breast Cancer Cells to Tamoxifen through Promoting Sirtuin 4

Evid Based Complement Alternat Med. 2022 Jan 15:2022:6730559. doi: 10.1155/2022/6730559. eCollection 2022.

Authors

Pei Zhang¹, Nan Wu², Zhi-Jun Song³, Zheng-Fu Tai⁴

Affiliations

¹ Yunnan Open University, Yunnan Vocational and Technical College of National Defense Industry, Kunming 650500, China.
² School of Medical, Yunnan University of Business Management, Kunming 650500, China.
³ Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China.
⁴ Sichuan Kelun Pharmaceutical Research Institute, Chengdu 610000, China.

Abstract

Tamoxifen is an effective drug for treating patients with advanced estrogen receptor-positive (ER+) breast cancer (BC), but not for all ER + BC patients. Drug tolerance is the biggest obstacle. In this study, we designed an experiment to investigate whether paeoniflorin affects the ER + BC cell's sensitivity to tamoxifen in the T47D and MCF-7 cell lines. Herein, we found that paeoniflorin inhibited cell proliferation without inducing apoptosis. However, it enhanced tamoxifen-induced apoptosis in both cell lines. Immunoblotting revealed that paeoniflorin significantly increased the already elevated Bax/Bcl2 protein expression ratio and the caspase 3 activity levels, both induced by tamoxifen. Paeoniflorin was also found to increase SIRT4 expression, and deletion of SIRT4 could significantly reverse the inhibition of cell proliferation induced by paeoniflorin and significantly decrease paeoniflorin-enhanced apoptosis induced by tamoxifen. Moreover, protein expression detection revealed that paeoniflorin enhanced the tamoxifen-induced inhibition of STAT3 activation. Besides, the deletion of SIRT4 could significantly increase STAT3 activation in the T47D and MCF-7 cells. In conclusion, paeoniflorin suppressed STAT3 activation to enhance the sensitivity of ER-positive breast cancer cells to tamoxifen through promoting SIRT4 expression.