Fujita Kyoko, Sano Daisuke, Kimura Machiko, Yamashita Yukiko, Kawakami Mariko, Ishiguro Yukari, Nishimura Goshi, Matsuda Hideki, Tsukuda Mamoru
Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Oncol Rep. 2007 Jul;18(1):47-51.
Human tumors are dependent on angiogenesis for growth, and the vascular endothelial growth factor (VEGF) is a major regulator of this process. Bevacizumab (Avastin), a monoclonal antibody directed against VEGF, has shown promise in treating a variety of cancers. In this study, we first examined the anti-tumor effects of bevacizumab on head and neck squamous cell carcinoma (HNSCC). Then we examined the effects of bevacizumab combined with paclitaxel, a chemotherapeutic agent, in HNSCC. This is the first demonstration of the anti-tumor effects of bevacizumab on HNSCC. In vitro, bevacizumab did not show any antiproliferative effects against the HNSCC cell lines. However, in vivo, bevacizumab showed dramatic anti-tumor effects against HNSCC tumor xenografts in mice. In addition, treatment with a bevacizumab-paclitaxel combination resulted in a remarkable inhibition of the HNSCC tumor xenografts, compared to the effects of each agent separately. A decreased blood vessel density and an increased apoptotic index were seen in the shrunken tumors. These results suggest that bevacizumab in combination with paclitaxel could have useful clinical application in HNSCC.
人类肿瘤的生长依赖于血管生成,而血管内皮生长因子(VEGF)是这一过程的主要调节因子。贝伐单抗(阿瓦斯汀)是一种针对VEGF的单克隆抗体,已显示出在治疗多种癌症方面的前景。在本研究中,我们首先检测了贝伐单抗对头颈部鳞状细胞癌(HNSCC)的抗肿瘤作用。然后我们检测了贝伐单抗联合化疗药物紫杉醇对HNSCC的影响。这是首次证明贝伐单抗对HNSCC具有抗肿瘤作用。在体外,贝伐单抗对HNSCC细胞系未显示出任何抗增殖作用。然而,在体内,贝伐单抗对小鼠HNSCC肿瘤异种移植显示出显著的抗肿瘤作用。此外,与单独使用每种药物的效果相比,贝伐单抗-紫杉醇联合治疗对HNSCC肿瘤异种移植产生了显著的抑制作用。在缩小的肿瘤中观察到血管密度降低和凋亡指数增加。这些结果表明,贝伐单抗联合紫杉醇可能在HNSCC中有实用的临床应用价值。