Abstract: Objective To investigate the effect of IFN-γ combined with IDO1 inhibitor Epacadostat(Epa) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with IFN-γ, Epa or IFN-γ combined with Epa on 4T1 and MDA-MB-231 cells for 48 h, the apoptosis of cells in each group was detected by flow cytometry. The expression of IDO1 was detected by Western blot and the yield of Kyn in 4T1or MDA-MB-231 cell lysate was detected by ELISA. The IDO1 was knocked out by using CRISPR-Cas9 system and knockout efficiency was examined by Western blot. Results IFN-γ showed a weaker killing effect on triple-negative breast cancer cells; IFN-γ significantly up-regulated the expression of IDO1 in triple-negative breast cancer cell lines (P＜0.001), and the level of Kyn in cell lysate was also significantly up-regulated (P＜0.01); cell apoptosis of IDO1 knock-out 4T1 (P＜0.01) or MDA-MB-231 (P＜0.01)cells treated with IFN-γ for 48 h was also significantly increased; IFN-γ combined with IDO1 inhibitor Epa promoted the apoptosis of 4T1 and MDA-MB-231 cells, and also prolonged the survival time of tumor-bearing mice. Conclusions The IDO1 inhibitor Epa might significantly enhance the therapeutic effect of IFN-γ on triple-negative breast cancer.

Key words: triple-negative breast cancer, IFN-γ, indoleamine 2,3-dioxygenase 1