MyD88 has been implicated in the tumourigenesis, metastasis and recurrence of breast cancer (BC). Here we utilized TJ-M2010-2 (TJ), an inhibitor of MyD88 homodimerimerization, and siMyD88 to suppress the function of MyD88 in MCF-7 and MDA-MB-231 cells. BC cells were treated in vitro and xenografted into nude mice to generate a model in vivo. TJ inhibited BC cell growth by impeding proliferation rather than by promoting apoptosis in vitro. Additionally, TJ and siMyD88 significantly attenuated cell migration and invasion, inhibited EMT-like progression and reduced cytokine (IL-6, IL-8, TGF-β1 and TNF-α) secretion induced by LPS. In vivo, TJ significantly hindered tumour growth in mice. Notably, TJ also decreased the secretion of IL-6, IL-8, TGF-β1, and TNF-α and M2 macrophage infiltration in the tumour microenvironment. The expression of MyD88, TRAF6, NF-κB p65, Snail, MMP-2, MMP-9, p-GSK-3β and p-Akt was significantly downregulated by TJ in BC cells and tumour tissues. Collectively, these results suggest that a MyD88 inhibitor (TJ) may be a promising therapeutic modality for treating BC patients.

MyD88与乳腺癌（BC）的肿瘤发生，转移和复发有关。在这里，我们利用MyD88均二聚化抑制剂TJ-M2010-2（TJ）和siMyD88来抑制MyD88在MCF-7和MDA-MB-231细胞中的功能。对BC细胞进行体外处理，并异种移植到裸鼠中以建立体内模型。TJ通过阻止增殖而不是通过促进体外凋亡来抑制BC细胞的生长。此外，TJ和siMyD88显着减弱了LPS诱导的细胞迁移和侵袭，抑制了EMT样进程并减少了细胞因子（IL-6，IL-8，TGF-β1和TNF-α）的分泌。体内，TJ明显阻碍了小鼠的肿瘤生长。值得注意的是，TJ还减少了肿瘤微环境中IL-6，IL-8，TGF-β1以及TNF-α和M2巨噬细胞浸润的分泌。TJ在BC细胞和肿瘤组织中显着下调MyD88，TRAF6，NF-κBp65，Snail，MMP-2，MMP-9，p-GSK-3β和p-Akt的表达。总体而言，这些结果表明，MyD88抑制剂（TJ）可能是治疗BC患者的一种有前途的治疗方式。