title: Beyond antiangiogenesis: intratumorally injected bevacizumab plays a cisplatin-sensitizing role in squamous cell carcinomas in mice.
abstract: BACKGROUND
  The anticancer mechanism of bevacizumab beyond antiangiogenesis remains unclear. Here, we investigated whether intratumorally injected bevacizumab could serve as an effective cisplatin sensitizer in squamous cell carcinoma (SCC) in vivo.
  
  
  METHODS
  Hela and SCC-VII experimental SCC models were established to investigate the anticancer effect of bevacizumab plus cisplatin and the underlying mechanism using immunostaining, TUNEL, and Western blot assays.
  
  
  RESULTS
  Bevacizumab-cisplatin therapy markedly inhibited tumor growth and significantly increased survival in both Hela- and SCC-VII-bearing mice compared with single-agent treatments and the untreated control, respectively. Immunostaining of CD34 showed that intratumorally injected bevacizumab significantly reduced microvessel density in bevacizumab-cisplatin and bevacizumab-alone groups of Hela xenografts. TUNEL assay showed that bevacizumab-cisplatin significantly promoted tumor cell apoptosis compared with single-agent treatments and untreated controls in these 2 models. Western blot showed that upregulation of cleaved caspase-3 and downregulation of Bcl-2 and p-Erk expressions are part of the molecular mechanisms beyond angiogenesis which contribute to the cooperative effect of bevacizumab plus cisplatin in the 2 SCC models.
  
  
  CONCLUSIONS
  Bevacizumab functions not only as an angiogenesis inhibitor but also as a chemosensitizer which enhances the cytotoxicity of cisplatin and promotes apoptosis of SCC cells.
authors: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China. kqwangyx@bjmu.edu.cn
authors: Yixiang
authors: Y
authors: Wang
authors: Ling
authors: L
authors: Dong
authors: Qingwei
authors: Q
authors: Bi
authors: Xiyuan
authors: X
authors: Ge
authors: Xiaoxia
authors: X
authors: Zhang
authors: Dengcheng
authors: D
authors: Wu
authors: Jia
authors: J
authors: Fu
authors: Chengfei
authors: C
authors: Zhang
authors: Cunyu
authors: C
authors: Wang
authors: Shenglin
authors: S
authors: Li