A cell-based high-throughput screen for epidermal growth factor receptor pathway inhibitors

Wen Hsing Lin, Jen Shin Song, Teng Yuan Chang, Chun Yu Chang, Yu Ning Fu, Chi Ling Yeh, Szu Huei Wu, Yu Wen Huang, Ming Yu Fang, Tzu Wen Lien, Hsing Pang Hsieh, Yu Sheng Chao, Shiu Feng Huang, Shih Feng Tsai, Lin Mei Wang, John T.A. Hsu, Yi Rong Chen

研究成果: Article同行評審

10 引文 斯高帕斯(Scopus)

摘要

Epidermal growth factor receptor (EGFR) is a valid drug target for development of target-based therapeutics against non-small-cell lung cancer. In this study, we established a high-throughput cell-based assay to screen for compounds that may inhibit EGFR activation and/or EGFR-mediated downstream signaling pathway. This drug screening platform is based on the characterization of an EGFR-transfected 32D cell line (32D-EGFR). The expression of EGFR in 32D cells allowed cell proliferation in the presence of either epidermal growth factor (EGF) or interleukin 3 (IL-3) and provided a system for both screening and counterscreening of EGFR pathway-inhibitory compounds. After the completion of primary and secondary screenings in which 32D-EGFR cells were grown under the stimulation of either EGF or IL-3, 9 of 20,000 compounds were found to selectively inhibit the EGF-dependent proliferation, but not the IL-3-dependent proliferation, of 32D-EGFR cells. Subsequent analysis showed that 3 compounds of the 9 initial hits directly inhibited the kinase activity of recombinant EGFR in vitro and the phosphorylation of EGFR in H1299 cells transfected with EGFR. Thus, this 32D-EGFR assay system provides a promising approach for identifying novel EGFR and EGFR signaling pathway inhibitors with potential antitumor activity.

原文English
頁(從 - 到)89-94
頁數6
期刊Analytical Biochemistry
377
發行號1
DOIs
出版狀態Published - 2008 六月 1

All Science Journal Classification (ASJC) codes

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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