Published in:
01-02-2009 | PRECLINICAL STUDIES
Antitumor activity of a novel EGFR tyrosine kinase inhibitor against human lung carcinoma in vitro and in vivo
Authors:
Xishan Xiong, Lili Fu, Li Wang, Houan Cai, Lin Li, Hualiang Jiang, Wenhu Duan, Changlin Mei
Published in:
Investigational New Drugs
|
Issue 1/2009
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Summary
Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has led to dramatic clinical improvement in selected patients with non-small cell lung cancer (NSCLC). However, intrinsic and acquired resistance to EGFR-TKI remains a common phenomenon. Novel EGFR-TKI, structurally different with erlotinib or gefitinib might be beneficial for patients with NSCLC. In this study, we examined the antitumor effect of a newly synthesized novel EGFR tyrosine kinase inhibitor (Zhao260054). In vitro studies in a panel of four different human lung cancer cell lines revealed that Zhao260054 inhibited cell proliferation with high potency and induced G0/G1 arrest of cell cycle and apoptosis. Zhao260054 markedly reduced phosphorylation of EGFR and inhibited activation of ERK1/2 and AKT. Oral administration of Zhao260054 (200 mg/kg/day) to BALB/c nude mice bearing SPC-A1 xenografts significantly retarded tumor growth. In conclusion, Zhao260054 has potent antitumor activity on human lung cancer in vitro and in vivo.