Antitumor activity of a novel EGFR tyrosine kinase inhibitor against human lung carcinoma in vitro and in vivo

作者：Xiong, Xishan; Fu, Lili; Wang, Li; Cai, Houan; Li, Lin; Jiang, Hualiang; Duan, Wenhu; Mei, Changlin^*

来源：Investigational New Drugs, 2009, 27(1): 1-11.

DOI：10.1007/s10637-008-9132-5

• EGFR
• SPC-A1
• tyrosine kinase inhibitor
• quinazoline
• non-small cell lung cancer

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 G(0)/G(1) 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.

• 出版日期2009-2
• 单位天津市中医药研究院附属医院; 新药研究国家重点实验室; 中国科学院上海药物研究所; 中国人民解放军第二军医大学