Research Paper Volume 14, Issue 17 pp 7156—7169
Combination of 7-O-geranylquercetin and microRNA-451 enhances antitumor effect of Adriamycin by reserving P-gp-mediated drug resistance in breast cancer
- 1 College of Pharmacy, Dalian Medical University, Dalian 116044, China
- 2 Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian 116001, China
- 3 The First Affiliated Hospital of Dalian Medical University, Dalian 116023, China
- 4 The Second Affiliated Hospital of Dalian Medical University, Dalian 116011, China
- 5 Affiliated Dalian Municipal Central Hospital of Dalian Medical University, Dalian 116033, China
- 6 Dalian Key Laboratory of Intelligent Blood Purification, Dalian 116033, China
Received: May 13, 2022 Accepted: September 5, 2022 Published: September 14, 2022https://doi.org/10.18632/aging.204287
How to Cite
Copyright: © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Although there are a lot of chemical drugs to treat breast cancer, increasing drug resistance of cancer cells has strongly hindered the effectiveness of chemotherapy. ATP-binding cassette transporters represented by P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) play an important role in drug resistance. This study aims to investigate the effect of 7-O-geranylquercetin (GQ) combining microRNA-451(miR-451) on reversing drug resistance of breast cancer and reveal the mechanism related to P-gp. Real-time RT-PCR and western blot assays showed that miR-326, miR-328, miR-451 and miR-155 inhibitor down-regulated the expression of genes MRP1, BCRP, MDR1 and the corresponding proteins MRP1, BCRP, P-gp, respectively. Cell counting kit-8 (CCK-8) assay indicated that these miRNAs reversed the resistance of MCF-7/ADR cells to Adriamycin (ADR), and miR-451 showed the greatest reversal effect. Combination of GQ and miR-451 enhanced the inhibitory effects of ADR on the proliferation and migration of MCF-7/ADR cells, and attenuated the expression of MDR1 and P-gp in MCF-7/ADR cells. A xenograft tumor model was used to show that GQ and miR-451 amplified the antitumor effect of ADR in nude mice, while western blot and immunohistochemical assays revealed the decreased expression of P-gp in tumor tissues. These results suggest that GQ and miR-451 have synergistic effect on reversing drug resistance through reducing the expression of MDR1 and P-gp in breast cancer MCF-7/ADR cells.