机构：[1]Department of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China[2]Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China[3]Changxing People’s Hospital of Zhejiang, Huzhou 313100, China[4]The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China[5]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Clinical Research Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[6]Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States[7]Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill 27599, North Carolina, United States
Exploring the mechanism through which berberine (Ber) reverses the multidrug resistance (MDR) of breast cancer is of great importance. Herein, we used the methyl thiazolyl tetrazolium assay to determine the drug resistance and cytotoxicity of Ber and doxorubicin (DOX) alone or in combination on the breast cancer cell line MCF-7/DOXFluc. The results showed that Ber could synergistically enhance the inhibitory effect of DOX on tumor cell proliferation in vitro, and the optimal combination ratio was Ber/DOX = 2:1. Using a luciferase reporter assay system combined with the bioluminescence imaging technology, the efflux kinetics of D-luciferin potassium salt in MCF-7/DOXFluc cells treated with Ber in vivo was investigated. The results showed that Ber could significantly reduce the efflux of D-luciferin potassium salt in MCF-7/DOXFluc cells. In addition, western blot and immunohistochemistry experiments showed that the expression of P-glycoprotein (P-gp/ABCB1) and multidrug resistance protein 1 (MRP1/ABCC1) in MCF-7/DOXFluc cells was downregulated upon Ber treatment. Finally, high-performance liquid chromatography was used to investigate the effect of Ber on DOX tissue distribution in vivo, and the results showed that the uptake of DOX in tumor tissues increased significantly when combined with Ber (P < 0.05). Thus, the results illustrated that Ber can reverse MDR by inhibiting the efflux function of ATP-binding cassette transporters and downregulating their expression levels.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81774011, 81473434, 81704082]; General research program of Zhejiang Provincial Department of health [2021KY813]; Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University (Traditional Chinese Pharmacology); Zhejiang Chinese Medical University [ZYAOXZD2019003]
第一作者机构：[1]Department of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China[2]Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China[2]Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China[*1]Department of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China[*2]Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
推荐引用方式(GB/T 7714)：
Qian Ke,Tang Chao-yuan,Chen Li-ying,et al.Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo[J].ACS OMEGA.2021,6(16):10645-10654.doi:10.1021/acsomega.0c06288.
APA：
Qian, Ke,Tang, Chao-yuan,Chen, Li-ying,Zheng, Shuang,Zhao, Yue...&Xiong, Yang.(2021).Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo.ACS OMEGA,6,(16)
MLA：
Qian, Ke,et al."Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo".ACS OMEGA 6..16(2021):10645-10654
