Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts.
Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor β. The present study investigated famitinib's activity against human gastric cancer cellsin vitroandin vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol -2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacyin vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growthin vivovia inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (>85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancerin vitroandin vivo, which may lay the foundations for future clinical trials.
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Sai
S
Ge
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Qiyue
Q
Zhang
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Qiong
Q
He
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Jianling
J
Zou
Central Laboratory, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Xijuan
X
Liu
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Na
N
Li
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Tiantian
T
Tian
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Yan
Y
Zhu
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Jing
J
Gao
Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Lin
L
Shen
antitumor activity; famitinib; gastric cancer; tyrosine kinase inhibitor