Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo.
Berberine Reverses Breast Cancer Multidrug Resistance Based on Fluorescence Pharmacokinetics In Vitro and In Vivo.
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小檗碱基于体外和体内荧光药代动力学逆转乳腺癌多药耐药性
DOI：
10.1021/acsomega.0c06288
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发表时间：
2021-04-27
期刊：
影响因子：
4.1
通讯作者：
Xiong Y
中科院分区：
文献类型：
--
作者：
Qian K;Tang CY;Chen LY;Zheng S;Zhao Y;Ma LS;Xu L;Fan LH;Yu JD;Tan HS;Sun YL;Shen LL;Lu Y;Liu Q;Liu Y;Xiong Y
探讨小檗碱逆转乳腺癌多药耐药的机制具有重要意义。在此，我们使用甲基噻唑基四唑测定来确定Ber和阿霉素（DOX）单独或组合对乳腺癌细胞系MCF-7/DOXFluc的耐药性和细胞毒性。结果表明，Ber能协同增强DOX对肿瘤细胞增殖的抑制作用，最佳组合比例为Ber/DOX = 2：1。利用荧光素酶报告基因系统结合生物发光成像技术，研究了Ber处理的MCF-7/DOXFluc细胞内钾盐中d-腺苷酸的外排动力学。结果表明，Ber能显著降低MCF-7/DOXFluc细胞钾盐中d-腺苷酸的外排。Western blot和免疫组化结果显示，Ber处理后MCF-7/DOXFluc细胞P-糖蛋白（P-gp/ABCB 1）和多药耐药蛋白1（MRP 1/ABCC 1）表达下调。最后，采用高效液相色谱法研究了Ber对DOX在体内组织分布的影响，结果表明，Ber与DOX联合用药后，肿瘤组织对DOX的摄取明显增加（P < 0.05）。因此，结果表明，Ber可以通过抑制ATP结合盒转运蛋白的外排功能和下调其表达水平来逆转MDR。
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.
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影响因子：
4.6
作者：
Bekele RT;Venkatraman G;Liu RZ;Tang X;Mi S;Benesch MG;Mackey JR;Godbout R;Curtis JM;McMullen TP;Brindley DN
通讯作者：
Brindley DN
影响因子：
5.2
作者：
Barbuti AM;Chen ZS
通讯作者：
Chen ZS
影响因子：
--
作者：
Liu S;Chen S;Yuan W;Wang H;Chen K;Li D;Li D
通讯作者：
Li D
影响因子：
3.6
作者：
Hermanson, David L.;Das, Sonia G.;Xing, Chengguo
通讯作者：
Xing, Chengguo
影响因子：
7.5
作者：
Scarfe L;Taylor A;Sharkey J;Harwood R;Barrow M;Comenge J;Beeken L;Astley C;Santeramo I;Hutchinson C;Ressel L;Smythe J;Austin E;Levy R;Rosseinsky MJ;Adams DJ;Poptani H;Park BK;Murray P;Wilm B
通讯作者：
Wilm B