Donkey milk inhibits tumor growth by inducing apoptosis, pyroptosis and modulation of Th1/Th2 responses in a 4T1 murine breast cancer model

[Display omitted] •Donkey milk (DM) induced tumor apoptosis and up-regulated the caspase-3/caspase-9/GSDME-mediated pyroptosis in 4 T1-derived tumors.•DM increased intratumoral CD8+ T cells and CD4+ T cells in a 4 T1 tumor-bearing mouse model.•DM elevated Th1/Th2 ratio and quelled immunosuppression from Tregs through inhibition of HDAC3/JAK2 −STAT3/5 and activation of STAT4 signaling pathways. Studies have demonstrated that donkey milk (DM) displays anti-tumor activity. In this study, we investigated the role and underlying mechanism of DM in the progression of 4T1 breast tumors in mice. We found that DM significantly reduced tumor volumes and tumor weights in 4T1-treated mice. Simultaneously, DM ameliorated the pathological changes in spleen, liver and lung tissues of 4T1 tumor-bearing mice. WB results showed that DM inducing the expression of Bax and pyroptosis-related proteins, and inhibiting the expression of Bcl-2 in tumors. Besides, DM up-regulation of Th1 cytokines and down-regulation of Th2/Treg cytokines in the tumors and spleen. Moreover, DM significantly decreased the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-STAT5/STAT5, as well as up-regulation the ratio of p-STAT4/STAT4 in tumors and spleen. Our data suggest that DM inhibit the growth of mouse 4T1 tumors by inducing apoptosis and pyroptosis, as well as promoting Th1 cell activation and quelling immunosuppression from Tregs.