Fig. 6

PepO enhances the anti-TNBC effect in combination with doxorubicin. A–C PY8119 bearing C57BL/6 mice were treated with PBS, PepO, doxorubicin (5 mg/kg), and the combination. The images of tumer (A), the tumor growth profiles (B) and tumor weight (C) were collected as shown (n = 6). D TUNEL staining of tumor tissues from each group was used to evaluate the apoptosis of tumor cells (scale bar = 1000 μm). Cell proliferation (Ki-67) was evaluated using Immunofluorescence detection (scale bar = 20 μm). E Model: PepO reprograms TAMs to anti-tumor M1 macrophages by activating PI3K-AKT-mTOR and inhibiting JAK2-STAT3 pathway via TLR2 / TLR4, consequently (1) Decrease the anti-inflammatory cytokines IL-10 and reverse the EMT process. (2) Enhance the functions of M1 macrophage related to cell killing, phagocytosis and NO biosynthetic process. (3) Increase the release of TNF-α, IL-6 and nitric oxide to promotes cancer cell apoptosis. Altogether, PepO suppresses the growth of TNBC. Two-way repeated-measures ANOVA with Sidak’s multiple comparisons test was used in (B). One-way ANOVA with Tukey’s multiple comparisons test was used in (C). Bar graphs represent mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001