The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways
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-beta 1 and TNF-alpha) 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-beta 1, and TNF-alpha and M2 macrophage infiltration in the tumour microenvironment. The expression of MyD88, TRAF6, NF-kappa B p65, Snail, MMP-2, MMP-9, p-GSK-3 beta 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.
基金：
National Natural Science Foundation of China [81802895]; Health and Family Planning Commission of Wuhan Municipality [WX17Q16]; Fundamental Research Funds for the Central Universities [2042019kf0229]
第一作者单位：[1]Wuhan Univ, Dept Breast & Thyroid Surg, Renmin Hosp, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Liu Jian-Hua,Chen Chuang,Li Ze-Yang,et al.The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways[J].EXPERIMENTAL CELL RESEARCH.2020,394(2):doi:10.1016/j.yexcr.2020.112157.
APA：
Liu, Jian-Hua,Chen, Chuang,Li, Ze-Yang,Zou, Zhi-Miao,Gao, Dong-Cheng...&Sun, Sheng-Rong.(2020).The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways.EXPERIMENTAL CELL RESEARCH,394,(2)
MLA：
Liu, Jian-Hua,et al."The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways".EXPERIMENTAL CELL RESEARCH 394..2(2020)
