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  • Title: [SUCI02 inhibits HER-2/neu receptor tyrosine kinase phosphorylation and growth of HER-2/neu-overexpressing breast cancer cells].
    Author: Zhu XF, Liu ZC, Xie BF, Cai LL, Yang DJ.
    Journal: Ai Zheng; 2003 Aug; 22(8):790-4. PubMed ID: 12917021.
    Abstract:
    BACKGROUND & OBJECTIVE: Overexpression of HER-2/neu receptor plays a key role in tumorigenesis,progression,prognosis and chemosensitivity of tumors. We found that SUCI02[N-(4-ethoyphenol)-2-hydroxy- acid amide] could inhibit HER2/neu phosphorylation through comprehensive screening. The aim of this study was to examine the effect of SUCI02 on HER-2/neu-overexpressing cancer cell growth. METHODS: Western blot analysis and immunoprecipitation was used to examine the changes of HER-2/neu receptor tyrosine kinase phosphorylation and protein level. MTT assay was employed to determine the growth inhibition of SUCI02 on the tumor cells. RESULTS: SUCI02 reversibly inhibited tyrosine phosphorylation of HER-2/neu in a dose-dependent manner with half maximal inhibition at a concentration of 4.34 microg/ml without reduced HER-2/neu receptor protein expression. Activation of MAPK and AKT, which were downstream molecules of HER-2/neu-mediated signal transduction pathway, was inhibited after being exposure to SUCI02. In contrast, tyrosine phosphorylation of EGFR was relatively unaffected at the concentrations of SUCI02 up to 40 microg/ml. SUCI02 inhibited cell proliferation of HER-2/neu- overexpressing MDA-MB-453m1 more potent than that of EGFR-overexpressing MDA-MB-468.Their IC(50) values were 1.33 microg/ml and 11.3 microg/ml,respectively. CONCLUSION: SUCI02 can inhibit tyrosine phosphorylation of HER-2/neu receptor,cell proliferation of HER-2/neu-overexpressing breast cancer cells preferentially and shut down downstream HER-2/neu signal transduction.
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