Shenzhen Laboratory of Tumor Cell Biology, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
School of Pharmacy, China Medical University, Shenyang 110122, China.
Int J Mol Sci. 2023 May 5;24(9):8265. doi: 10.3390/ijms24098265.
Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes and , and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.
三阴性乳腺癌（TNBC）已被明确视为乳腺癌（BC）亚型中预后最差的异质性肿瘤。目前治疗 TNBC 的小分子药物及其他新型抑制剂的出现和应用，使 TNBC 的治疗选择更具选择性。然而，仍存在一些问题，如患者耐受性差、给药剂量大、给药频率高、毒副作用大等，因此需要开发更有效、毒性更低的治疗策略。Nrf2 是一种重要的抗氧化转录因子，其高表达常促进肿瘤进展，也是 BC 治疗中最有效的靶点之一。我们发现，在 MDA-MB-231 细胞和 SUM159 细胞中，白头翁素（BRU）联合虎杖苷（PD）可显著抑制体外细胞增殖，显著下调 Nrf2 蛋白及其下游相关靶基因和的表达，并促进活性氧（ROS）水平，从而进一步增强抗肿瘤作用。此外，我们在体内实验中发现，通过将药物剂量减少三分之一，可以显著抑制肿瘤细胞生长，同时避免毒副作用，为 TNBC 治疗提供了一种更具临床应用价值的治疗方法。
