期刊
CANCER LETTERS
卷 493, 期 -, 页码 189-196出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.08.041
关键词
Breast cancer; Sulforaphane; Doxorubicin; CD8(+) T cells; Myeloid-derived suppressor cells
类别
资金
- Improvement Project for Theranostic ability on Difficulty Miscellaneous disease (Tumor) [ZLYNXM202008]
- Science & Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University [znpy2016095, znpy2018027]
- National Natural Science Foundation of China [81702627]
- Medical Talented Youth Development Project of the Health Commission of Hubei Province [WJ2019Q049]
- Sixth Training Program Foundation for Wuhan Medical Talents by the Health Commission of Wuhan
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.
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