title: Axitinib alone or in combination with chemotherapeutic drugs exerts potent antitumor activity against human gastric cancer cells in vitro and in vivo.
abstract: OBJECTIVE
  As the new oral selective VEGFR tyrosine kinase inhibitor, axitinib (AG-013736) exerts powerful antitumor activity in multiple solid tumors, while its' effect was unclear in gastric cancer. We aimed to investigate the antitumor activity of axitinib alone or combined with chemotherapeutic drugs against human gastric cancer cells in vitro and in vivo.
  
  
  METHODS
  The IC50 values of drugs were determined by MTS assay. The median effect of Chou-Talalay was used to assess the synergistic effect of two drugs. Flow cytometry was employed to analyze cell cycle and cell apoptosis. Cell senescence and microvessel density were evaluated by SA-β-gal staining and CD34 staining, respectively. BGC-823-derived xenografts in nude mice were established to investigate the effects of drugs in vivo.
  
  
  RESULTS
  Axitinib alone could inhibit cell proliferation and retard tumor growth through inducing cell cycle arrest at G2/M phase, cell senescence, cell apoptosis, and antiangiogenesis in vitro and in vivo. Axitinib combined with 5-fluorouracil (5-FU) had synergistic inhibitory effect compared to axitinib or 5-FU alone. However, the highest inhibitory effect was found between axitinib and cisplatin (inhibitory ratio >80 % compared to control), which was significantly higher than any single drug (inhibitory ratio for single 5-FU, cisplatin, and axitinib >10, >40, and >40 %, respectively, compared to control) or axitinib combined with 5-FU (inhibitory ratio >50 % compared to control).
  
  
  CONCLUSIONS
  We highlighted for the first time that axitinib alone or in combination with 5-fluorouracil or cisplatin has potent antitumor activity against human gastric cancer in vitro and in vivo, which provided solid evidence for future clinical trial.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing, 100142, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Sai
authors.initials: S
authors.lastname: Ge
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Peng
authors.forename: Yilin
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077784:Axitinib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; D002945:Cisplatin; D005472:Fluorouracil