IR@PKUHSC  > 北京大学基础医学院  > 病理学系
学科主题基础医学
Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells
Zhang, Yun-Gang1,2; Du, Qiang1; Fang, Wei-Gang1; Jin, Mu-Lan2; Tian, Xin-Xia1
关键词breast cancer epidermal growth factor receptor Tyrphostin AG1478
刊名INTERNATIONAL JOURNAL OF ONCOLOGY
2008-09-01
DOI10.3892/ijo_00000045
33期:3页:595-602
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
资助者National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China
研究领域[WOS]Oncology
关键词[WOS]GROWTH-FACTOR-RECEPTOR ; TYROSINE KINASE INHIBITOR ; CARCINOMA-CELLS ; TELOMERASE ACTIVITY ; PANCREATIC-CANCER ; EPITHELIAL-CELLS ; DRUG-RESISTANCE ; LUNG-CANCER ; PHASE-II ; EXPRESSION
英文摘要

Inhibition of epidermal growth factor receptor (EGFR) signaling is a promising treatment strategy for malignant tumors. In this study, we evaluated the effectiveness of Tyrphostin AG1478, a potent and specific inhibitor of EGFR tyrosine kinase, on the growth, apoptosis and invasion of breast cancer cells. Western blotting demonstrated that AG1478 inhibited the phosphorylation of EGFR, ERK1/2 and AKT in a dose-dependent manner. Three proliferation analyses, MTT, cell counting, and clone formation assay, consistently showed that AG1478 significantly inhibited cell proliferation in a dose-dependent manner. FACS analysis demonstrated that AG1478 promoted cell apoptosis. In addition, TRAP assay exhibited that AG1478 significantly suppressed telomerase activity of tumor cells, which was parallel with growth inhibition. Semi-qantitative RT-PCR revealed that the suppression of telomerase activity was correlated with the decreased expression of human telomerase catalytic subunit (hTERT) mRNA, the rate-limiting determinant of its enzyme activity. These data suggest that AG1478 suppressed cellular growth by inhibiting cellular proliferation, inducing apoptosis and inhibiting telomerase activity. Furthermore, we also examined the effects of AG1478 on cellular invasion. Boyden chamber invasion assay showed that AG1478 significantly inhibited cell invasion in a dose-dependent manner. Western blotting revealed that AG1478 could down-regulate the expression of MMP-9, which may be one of the mechanisms by which AG1478 suppressed cellular invasion. In conclusion, this study demonstrated that Tyrphostin AG1478 effectively inhibited the proliferation and invasion of breast cancer cells. Tyrphostin AG1478 may be a potential EGFR-targeted therapeutic agent for breast cancer.

语种英语
所属项目编号30670805 ; 30770829
资助者National Natural Sciences Foundation of China ; National Natural Sciences Foundation of China
WOS记录号WOS:000259519500022
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58723
专题北京大学基础医学院_病理学系
作者单位1.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China
2.Capital Med Univ, Beijing Chao Yang Hosp, Dept Pathol, Beijing 100020, Peoples R China
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GB/T 7714
Zhang, Yun-Gang,Du, Qiang,Fang, Wei-Gang,et al. Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2008,33(3):595-602.
APA Zhang, Yun-Gang,Du, Qiang,Fang, Wei-Gang,Jin, Mu-Lan,&Tian, Xin-Xia.(2008).Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells.INTERNATIONAL JOURNAL OF ONCOLOGY,33(3),595-602.
MLA Zhang, Yun-Gang,et al."Tyrphostin AG1478 suppresses proliferation and invasion of human breast cancer cells".INTERNATIONAL JOURNAL OF ONCOLOGY 33.3(2008):595-602.
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