Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.
Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.
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黑米花青素通过靶向 RAS/RAF/MAPK 通路抑制乳腺癌细胞转移
DOI：
10.1155/2015/414250
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发表时间：
2015
影响因子：
--
通讯作者：
Yu XP
中科院分区：
文献类型：
--
作者：
Chen XY;Zhou J;Luo LP;Han B;Li F;Chen JY;Zhu YF;Chen W;Yu XP
人类表皮生长因子受体2(HER2)的过度表达导致了30%的乳腺癌病例的生物学行为。Ras/RAF/MAPK通路作为HER2信号转导通路，在乳腺癌的发生发展中起着关键作用。在这项研究中，我们研究了黑米花青素(BRACs)提取物化学预防作用的分子机制，并确定了它们在HER2+乳腺癌细胞中的分子靶点。BRACs作用于MDA-MB-453细胞(HER2+)可抑制细胞迁移和侵袭，抑制丝裂原活化蛋白激酶(RAF)、丝裂原活化蛋白激酶(MEK)和c-jun氨基末端激酶(JNK)的激活，并下调基质金属蛋白酶2(MMP2)和MMP9的分泌。Bracs还分别减弱了HER2与RAF、MEK和JNK蛋白的相互作用，并降低了RAF、MEK和JNK的mRNA表达。此外，我们发现BRACs与RAF、MEK或JNK抑制剂联合治疗可以增强抗转移活性。瞬时转染针对RAF、MEK和JNK的小干扰RNA(SiRNAs)可抑制其在MDA-MB-453细胞中的表达。此外，BRACs和siRNA联合作用时，抑制作用比单独作用时更明显。综上所述，我们的研究表明BRAC通过靶向RAS/RAF/MAPK通路来抑制乳腺癌细胞的转移。
Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2+ breast cancer cells. Treatment of MDA-MB-453 cells (HER2+) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.