Suppressing M2 Macrophage Polarization by Glycine Combined with β-Elemene via the IL-6/JAK2/STAT3 Signaling Pathway to Inhibit Triple-Negative Breast Cancer Progression.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, closely associated with an imbalanced tumor immune microenvironment. Tumor-associated macrophages (TAMs) play a crucial role in tumor progression. Purpose: This study aimed to investigate whether glycine combined with β-elemene inhibits TNBC progression by suppressing M2 macrophage polarization through the IL-6/JAK2/STAT3 pathway. Methods: UPLC-Q-Exactive HRMS was used to identify glycine and β-elemene. In vitro, 4T1 cell viability was determined by CCK-8 assay. RAW264.7 cells were polarized to M2 macrophages and co-cultured with 4T1 cells. Colony formation, wound healing, and Transwell assays were performed. Western blot and immunohistochemistry were used to detect protein expression. In vitro experiments were performed with at least three independent biological replicates. In vivo, 4T1 xenograft mouse models were established (n=10 per group) to evaluate anti-tumor efficacy. Results: Glycine combined with β-elemene significantly suppressed proliferation, colony formation, and migration of 4T1 cells. Mechanistically, the combination inhibited M2 macrophage polarization by downregulating IL-6, p-JAK2, and p-STAT3. In vivo, the combination with paclitaxel showed the strongest anti-tumor effect, with reduced tumor volume and weight, decreased Ki-67 expression, and suppressed M2 polarization. Conclusion: Glycine combined with β-elemene inhibits M2 macrophage polarization by suppressing the IL-6/JAK2/STAT3 pathway, thereby exerting anti-TNBC effects. Its combination with paclitaxel demonstrates synergistic anti-tumor efficacy.