The occurrence of multidrug resistance (MDR) is one of the impediments in the clinical treatment of breast cancer, and MDR breast cancer has abnormally high breast cancer resistance protein (BCRP/ABCG2) expression. However, there are currently no clinical drugs that inhibit this target. Our previous study found that 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ0814061/SQ), a small molecule drug with low toxicity to normal tissues, could target microtubules, inhibit the proliferation of breast cancer, and reduce its migration and invasion abilities. However, the effect and the underlying mechanism of SQ on MDR breast cancers are still unknown. Therefore, in this study, we investigated the effect of SQ on adriamycin-resistant MCF-7 (MCF-7/ADR) cells and explored the underlying mechanism. The MTT assay showed that SQ had potent cytotoxicity to MCF-7/ADR cells. In particular, the results of western blot and flow cytometry proved that SQ could effectively inhibit the expression of BCRP in MCF-7/ADR cells to decrease its drug delivery activity. In addition, SQ could block the cell cycle at G2/M phase in parental and MCF-7/ADR cells, thereby mediating cell apoptosis, which was related with the inhibition of PI3K-Akt-MDM2 pathway. Taken together, our findings indicate that SQ overcomes multidrug resistance in MCF-7/ADR cells by inhibiting BCRP function and mediating apoptosis through PI3K-Akt-MDM2 pathway inhibition.

多药耐药（MDR）的发生是乳腺癌临床治疗的障碍之一，MDR乳腺癌的乳腺癌耐药蛋白（BCRP/ABCG2）表达异常高。然而，目前尚无抑制该靶点的临床药物。我们前期的研究发现，2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl)phenol (SQ0814061/SQ)是一种对正常组织低毒的小分子药物，可以靶向微管，抑制乳腺癌的增殖，并降低其迁移和入侵能力。然而，SQ 对 MDR 乳腺癌的影响和潜在机制仍然未知。因此，在本研究中，我们研究了 SQ 对耐阿霉素 MCF-7 (MCF-7/ADR) 细胞的影响，并探讨了其潜在机制。MTT检测显示SQ对MCF-7/ADR细胞具有较强的细胞毒性。特别是western blot和流式细胞仪的结果证明，SQ能有效抑制MCF-7/ADR细胞中BCRP的表达，降低其给药活性。此外，SQ可以阻断亲代细胞和MCF-7/ADR细胞G2/M期的细胞周期，从而介导细胞凋亡，这与抑制PI3K-Akt-MDM2通路有关。总之，我们的研究结果表明，SQ 通过抑制 BCRP 功能和通过 PI3K-Akt-MDM2 通路抑制介导细胞凋亡来克服 MCF-7/ADR 细胞的多药耐药性。SQ可以阻断亲代细胞和MCF-7/ADR细胞G2/M期的细胞周期，从而介导细胞凋亡，这与抑制PI3K-Akt-MDM2通路有关。总之，我们的研究结果表明，SQ 通过抑制 BCRP 功能和通过 PI3K-Akt-MDM2 通路抑制介导细胞凋亡来克服 MCF-7/ADR 细胞的多药耐药性。SQ可以阻断亲代细胞和MCF-7/ADR细胞G2/M期的细胞周期，从而介导细胞凋亡，这与抑制PI3K-Akt-MDM2通路有关。总之，我们的研究结果表明，SQ 通过抑制 BCRP 功能和通过 PI3K-Akt-MDM2 通路抑制介导细胞凋亡来克服 MCF-7/ADR 细胞的多药耐药性。