Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells.
Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells.
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DOI：
10.1016/j.lfs.2012.03.035
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发表时间：
2012-05
期刊：
影响因子：
6.1
通讯作者：
Ning-ning Zhou;Jun Tang;Wen-dan Chen;G. Feng;B. Xie;Z. Liu;Dajun Yang;Xiao-Feng Zhu
中科院分区：
文献类型：
--
作者：
Ning-ning Zhou;Jun Tang;Wen-dan Chen;G. Feng;B. Xie;Z. Liu;Dajun Yang;Xiao-Feng Zhu
目的HER2/neu受体的过度表达在肿瘤的发生、发展中起关键作用。靶向HER2/neu的小分子对过度表达HER2的癌症具有治疗价值。本研究探讨了中草药鱼腥草中的鱼腥草素对HER2/neu酪氨酸磷酸化及其体内抗肿瘤活性的影响。采用四甲基偶氮唑盐比色法检测对细胞增殖的抑制作用。鱼腥草素可剂量依赖性地抑制HER2的磷酸化，其IC50值为5.52μg/ml，但不影响HER2/neu蛋白的表达。鱼腥草素还抑制HER2/neu介导的信号转导通路下游分子ERK1/2和AKT的激活。相反，当鱼腥草素浓度增加到40μg/ml时，A431细胞和mda-MB-468细胞中EGFR的酪氨酸磷酸化均不受影响。此外，鱼腥草素优先抑制过表达HER2/neu的MDA-MB-453细胞的生长；过表达EGFR的MDA-MB-468细胞不受影响。在BT474和N87移植瘤中，给予鱼腥草素显著降低HER2的磷酸化水平和肿瘤体积，两者均过表达HER2/neu。这种药物可能在治疗HER2/neu过表达的癌症方面提供治疗价值。
AIMSThe overexpression of HER2/neu receptor plays a key role in tumorigenesis and tumor progression. Small molecules targeting HER2/neu have therapeutic value in cancers that overexpress HER2. In this present study, the effect of houttuyninum, a component in the Chinese herbal medicine Houttuynia cordata Thunb, on HER2/neu tyrosine phosphorylation and its in vivo antitumour activity was investigated.MAIN METHODSThe phosphorylation and expression of proteins were determined by Western blot analysis. The MTT assay was employed to examine the inhibition of cell proliferation in vitro. Xenografts were established in nude mice for evaluating the antitumour activity of houttuyninum in vivo.KEY FINDINGSHouttuyninum inhibited phosphorylation of HER2 in a dose-dependent manner with an IC50 of 5.52μg/ml without reducing HER2/neu protein expression in MDA-MB-453 cells. Houttuyninum also inhibited the activation of ERK1/2 and AKT, downstream molecules in the HER2/neu-mediated signal transduction pathway. In contrast, tyrosine phosphorylation of EGFR was unaffected when the concentration of houttuyninum was increased to 40μg/ml in both A431 cells and MDA-MB-468 cells. Additionally, houttuyninum preferentially inhibited the growth of MDA-MB-453 cells that overexpressed HER2/neu; the MDA-MB-468 cells that overexpress EGFR remained unaffected. Administration of houttuyninum in vivo resulted in a significant reduction of phosphorylated HER2 levels and in tumor volumes of the BT474 and N87 xenografts, which both overexpress HER2/neu.SIGNIFICANCEOur findings showed that houttuyninum can inhibit the HER2/neu signalling pathway and the tumor growth of cancer cells that overexpress HER2/neu. This drug may provide therapeutic value in the treatment of cancers that involve overexpression of HER2/neu.