Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling activation
Oxymatrine reverses epithelial-mesenchymal transition in breast cancer cells by depressing α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling activation
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发表时间：
2019
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通讯作者：
Yan Chen;Lin Chen;Jing-Yue Zhang;Zong-yue Chen;Tingting Liu;Yanyun Zhang;Ling-yun Fu;Shuangqin Fan;Minqin Zhang;Shi-quan Gan;Nengpan Zhang;Xiangfeng Shen
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作者：
Yan Chen;Lin Chen;Jing-Yue Zhang;Zong-yue Chen;Tingting Liu;Yanyun Zhang;Ling-yun Fu;Shuangqin Fan;Minqin Zhang;Shi-quan Gan;Nengpan Zhang;Xiangfeng Shen
逆转乳腺癌细胞中的EMT，并探索潜在的分子机制。材料与方法：MTT法检测细胞活力。伤口愈合实验和transwell小室实验分别用于评估细胞的迁移和侵袭。免疫荧光和Western blot检测EMT相关分子的表达及α Ⅴ β 3整合素/粘着斑激酶（FAK）/磷脂酰肌醇3激酶（PI 3 K）/蛋白激酶B（Akt）信号转导。纤连蛋白是α Ⅴ β 3整合素的生理配体，用于刺激α Ⅴ β 3整合素信号传导。结果如下：我们的结果表明，氧化苦参碱有效地抑制MDA-MB-231和4 T1乳腺癌细胞的活力，氧化苦参碱对正常乳腺乳腺上皮MCF-10A细胞的细胞毒性较小。此外，氧化苦参碱在无毒浓度下逆转MDA-MB-231和4 T1细胞中的EMT。氧化苦参碱可显著抑制MDA-MB-231和4 T1细胞的迁移和侵袭，下调N-cadherin、vimentin和Snail的表达，上调4 T1细胞E-cadherin的表达。氧化苦参碱降低α Ⅴ和β 3整合素的表达及其共定位。它还通过抑制FAK、PI 3 K和Akt的磷酸化来抑制α Ⅴ β 3整合素下游活化。此外，氧化苦参碱可抑制纤连蛋白诱导的EMT和α Ⅴ β 3整合素/FAK/PI 3 K/Akt信号通路的激活。结论：结果表明，氧化苦参碱通过抑制α Ⅴ β 3整合素/FAK/PI 3 K/Akt信号通路，有效逆转乳腺癌细胞EMT。因此，氧化苦参碱可能是一个潜在的治疗候选人与抗转移的潜力，用于治疗乳腺癌。
reverses EMT in breast cancer cells and to explore the underlying molecular mechanisms. Materials and methods: MTT assay was performed to evaluate cell viability. Wound-healing assay and transwell chamber assay were used to assess cell migration and invasion, respectively. Immuno fl uorescence and Western blot were used to study the expression of EMT-related molecules and α Ⅴ β 3 integrin/focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling transduction. Fibronectin, a physiologic ligand of α Ⅴ β 3 integrin, was used to stimulate α Ⅴ β 3 integrin signaling. Results: Our results demonstrated that oxymatrine effectively suppressed the viability of MDA-MB-231 and 4T1 breast cancer cells, and oxymatrine showed less cytotoxicity on normal breast mammary epithelial MCF-10A cells. In addition, oxymatrine reversed EMT in the MDA-MB-231 and 4T1 cells at nontoxic concentrations. Oxymatrine signi fi cantly inhibited cell migration and invasion, downregulated the expression of N-cadherin, vimentin, and Snail in MDA-MB-231 and 4T1 cells, but upregulated the expression of E-cadherin in 4T1 cells. The mechanism revealed that oxymatrine decreased the expression of α Ⅴ and β 3 integrin and their co-localization. It also inhibited α Ⅴ β 3 integrin downstream activation by suppressing the phosphorylation of FAK, PI3K, and Akt. Furthermore, oxymatrine prevented fi bronectin-induced EMT and α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling activation. Conclusion: Our results revealed that oxymatrine effectively reversed EMT in breast cancer cells by depressing α Ⅴ β 3 integrin/FAK/PI3K/Akt signaling. Thus, oxymatrine could be a potential therapeutic candidate with anti-metastatic potential for the treatment of breast cancer.