StemRegenin-1 Reverses Drug Resistance of MCF-7/ADR Cells via AhR/ABC Transports and AhR/UGTs Pathways

被引：2
作者：
Zhang, Yang [1 ,2 ]
Ma, Yu-Chen [3 ]
Song, Jue [1 ,2 ]
Jin, Yong [1 ,2 ]
Bao, Yan-Ni [4 ]
机构：
[1] Anhui Med Univ, Sch Pharm, Key Lab Antiinflammatory & Immune Med, Minist Educ, Hefei 230032, Peoples R China
[2] Anhui Med Univ, Sch Pharm, Inflammat & Immune Mediated Dis Lab Anhui Prov, Hefei 230032, Peoples R China
[3] Fuyang Canc Hosp, Dept Med Oncol, Fuyang, Anhui, Peoples R China
[4] Linyi Higher Specialized Affiliated Hosp, 80 Jintan Rd, Linyi 276002, Shandong, Peoples R China
来源：
CURRENT PROTEOMICS | 2024年 / 21卷 / 02期
关键词：
Breast cancer; aryl hydrocarbon receptor (AhR); MCF-7/ADR cells; StemRegenin-1 (SR-1); Adriamycin (ADM); ARYL-HYDROCARBON RECEPTOR; BREAST-CANCER; MULTIDRUG-RESISTANCE; UDP-GLUCURONOSYLTRANSFERASES; HUMAN ABSORPTION; CHEMOTHERAPY; EXPRESSION; METABOLISM; EXCRETION; ACTIVATOR;
D O I：
10.2174/0115701646317215240712103448
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Objectives Drug resistance reduces the antitumor efficacy of chemotherapy. Therefore, it is important to know how to reverse drug resistance. In this work, we investigated drug resistance reversal by StemRegenin-1(SR-1) in MCF-7/ADR cells and the mechanism by which it exerts its drug resistance effect. Methods MTT test and protein blot were employed as the two main in vitro cell tests. The cells were treated with SR-1 and ADM to detect the changes in their proteomics, and then the effects of AhR downstream proteins, glucuronidase, and drug-resistant proteins were verified. The accumulation of ADM in the combined cells and its effect on the cell cycle were detected by flow cytometry. In vivo, a BALB/C mice xenograft test was conducted to observe the anti-tumor effect and side effects of the drug combination. Results SR-1 combined with ADM inhibited cell proliferation and significantly decreased the expression of CYP1A1, UGT1A6, P-gP (ABCB1), and MRP1 (ABCC1). Furthermore, SR-1 caused apoptosis and cell cycle arrest. In vivo experiments showed that SR-1 significantly enhanced the antitumor effects of ADM and reduced the toxic effects of ADM. Conclusion SR-1 inhibited AhR activity, decreased its downstream protein CYP1A1 and the expression of UGT1A6, P-gP, and MRP1 in MCF-7/ADR cells, and reversed drug resistance in MCF-7/ADR cells through AhR/ABC transports and AhR/UGTs pathways.
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页码：113 / 128
页数：16
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