Sulforaphane (SFN) is a compound derived from cruciferous plants shown to be effective in cancer prevention and suppression. Myeloid-derived suppressor cells (MDSCs) are known to inhibit anti-tumor immunity; however, whether SFN regulates the anti-tumor activity of MDSCs in breast cancer is still unknown. In the current study, we found that SFN blocked prostaglandin E2 (PGE2) synthesis in parental and doxorubicin (DOX)-resistant breast cancer 4T1 cell lines by activating NF-E2-related factor 2 (Nrf2). Nrf2-mediated reduction of PGE2 was dependent on the enhanced expression of heme oxygenase 1 (HO-1) and glutamate-cysteine ligase (GCLC), and decreased COX-2 expression in breast cancer cells. Moreover, our study further revealed that reduced PGE2 secretion from SFN-treated 4T1 cells triggered MDSCs to switch to an immunogenic phenotype, enhancing the anti-tumor activities of CD8⁺ T cells. Co-administration of SFN and DOX was more efficacious for the treatment of breast cancer in a mouse model than either agent alone, as evidenced by the significant decrease in tumor volume, MDSC expansion, and increase in cytotoxic CD8⁺ T cells. Taken together, our data indicate that SFN reverses the immunosuppressive microenvironment and is a potent adjuvant chemotherapeutic candidate in breast cancer.

萝卜硫素（SFN）是一种来自十字花科植物的化合物，被证明对预防和抑制癌症有效。已知骨髓来源的抑制细胞（MDSCs）抑制抗肿瘤免疫。但是，SFN是否调节乳腺癌中MDSC的抗肿瘤活性仍是未知的。在当前的研究中，我们发现SFN通过激活NF-E2相关因子2（Nrf2）阻断了亲本和对阿霉素（DOX）耐药的乳腺癌4T1细胞系中的前列腺素E2（PGE2）合成。Nrf2介导的PGE2减少取决于血红素加氧酶1（HO-1）和谷氨酸半胱氨酸连接酶（GCLC）的表达增强，以及COX-2在乳腺癌细胞中的表达降低。此外，我们的研究进一步表明，经SFN处理的4T1细胞的PGE2分泌减少会触发MDSC转变为免疫原性表型，⁺ T细胞。SFN和DOX的共同给药比单独使用任何一种药物对小鼠模型的乳腺癌治疗更为有效，这可通过肿瘤体积，MDSC扩张和细胞毒性CD8 ⁺ T细胞的显着减少来证明。综上所述，我们的数据表明SFN可以逆转免疫抑制微环境，并且是乳腺癌的有效辅助化疗药物。