秦皮素通过抑制EGFR及其下游AKT信号通路抑制MCF-7细胞增殖及迁移

Fraxetin Inhibits MCF-7 Cell Proliferation and Migration through Inhibiting EGFR and Its Downstream AKT Signaling Pathway

表皮生长因子受体(EGFR)是细胞内多种信号调节通路的交汇点,其介导的信号通路与乳腺癌的发生、发展、转移和侵袭等密切相关,已成为乳腺癌治疗的新靶点之一。但目前关于秦皮素的抗乳腺癌作用与EGFR通路的关系,国内外尚未见相关报道。本研究结果表明,秦皮素能够通过抑制EGFR及其下游的AKT信号通路来发挥其抗乳腺癌作用。秦皮素在体外可促进T、B淋巴细胞增殖及巨噬细胞吞噬能力,提示秦皮素可能促进小鼠免疫功能。Western印迹结果表明,秦皮素能显著抑制EGFR蛋白及其下游的AKT蛋白磷酸化水平。划痕实验结果表明,秦皮素能抑制MCF-7细胞的迁移。此外,秦皮素还能促进小鼠巨噬细胞的吞噬能力和代谢活力,促进T、B淋巴细胞的增殖,提高NK细胞的杀伤活力。本研究结果提示,秦皮素的抗乳腺癌作用是通过抑制EGFR信号通路,抑制MCF-7细胞迁移和促进小鼠的免疫功能等多种途径来实现的。

epidermal growth factor receptor（ EGFR） is an intersection of various of signaling pathways in cells,its signaling pathway is closely related with occurrence,development,metastasis and invasion of breast cancer,it has become one of new targets of breast cancer treatment. However,its anti-breast cancer mechanisms and relationship with EGFR signaling pathway were poorly studied. Our research indicated that,the anti-breast cancer activity of fraxetin mainly is to inhibit EGFR and its downstream AKT signaling pathway,fraxetin could promote the proliferation of T,B lymphocyte and improve the phagocytosis of macrophage in vitro,indicating that fraxetin could promote immune function in mice.Western blotting results indicated that fraxetin could inhibit the expression and activation of EGFR and AKT. Wound healing assay result showed that fraxetin could inhibit cell migration. In addition,fraxetin could significantly improve the immune function and the phagocytosis of macrophage, increase the proliferation of T,B lymphocyte and improve the killing activity of NK cells. The results suggested that the anti-breast cancer effects of fraxetin were inhibited cell migration,promoted the proliferation of T,Blymphocyte and improved the phagocytosis of macrophage and killing activity of NK cells through the EGFR and AKT signaling pathway.