Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells.
Aloe-emodin inhibits HER-2 expression through the downregulation of Y-box binding protein-1 in HER-2-overexpressing human breast cancer cells.
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DOI：
10.18632/oncotarget.10410
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Way TD
中科院分区：
文献类型：
--
作者：
Ma JW;Hung CM;Lin YC;Ho CT;Kao JY;Way TD
人表皮生长因子受体-2（HER-2）阳性乳腺癌往往具有侵袭性、高转移性和耐药性，并迅速扩散。研究表明大黄素抑制HER-2的表达。本研究比较了两种大黄提取物芦荟大黄素（AE）和大黄酸对HER-2的抑制作用。我们的结果表明，AE对HER-2表达的抑制作用最强。用AE治疗HER-2过表达的乳腺癌细胞减少了肿瘤发生、细胞迁移和细胞侵袭。AE能够抑制YB-1表达，进一步抑制下游HER-2表达。AE通过抑制HER-2过表达乳腺癌细胞中的Twist来抑制YB-1表达。我们的数据还发现AE通过抑制EMT来抑制癌症转移和癌症干细胞。有趣的是，在HER-2过表达的乳腺癌细胞中，AE通过下调细胞内整合素连接激酶（ILK）/蛋白激酶B（Akt）/mTOR信号通路抑制YB-1表达。体内实验表明，AE对HER-2过表达乳腺癌细胞的裸鼠移植瘤有明显的抗肿瘤作用。这些发现提示AE在HER-2阳性乳腺癌治疗中的可能应用。
Human epidermal growth factor receptor-2 (HER-2)-positive breast cancer tends to be aggressive, highly metastatic, and drug resistant and spreads rapidly. Studies have indicated that emodin inhibits HER-2 expression. This study compared the HER-2-inhibitory effects of two compounds extracted from rhubarb roots: aloe-emodin (AE) and rhein. Our results indicated that AE exerted the most potent inhibitory effect on HER-2 expression. Treatment of HER-2-overexpressing breast cancer cells with AE reduced tumor initiation, cell migration, and cell invasion. AE was able to suppress YB-1 expression, further suppressing downstream HER-2 expression. AE suppressed YB-1 expression through the inhibition of Twist in HER-2-overexpressing breast cancer cells. Our data also found that AE inhibited cancer metastasis and cancer stem cells through the inhibition of EMT. Interestingly, AE suppressed YB-1 expression through the downregulation of the intracellular integrin-linked kinase (ILK)/protein kinase B (Akt)/mTOR signaling pathway in HER-2-overexpressing breast cancer cells. In vivo study showed the positive result of antitumor activity of AE in nude mice injected with human HER-2-overexpressing breast cancer cells. These findings suggest the possible application of AE in the treatment of HER-2-positive breast cancer.