Effects of hypoxia-targeted therapies combined with chemo-radio therapy in oral squamous cell carcinoma cells

研究了一氧化氮（NO）供体对化疗药物对口腔鳞状细胞癌（OSC）细胞抗肿瘤活性的影响。在常氧和缺氧条件下，5-FU与NO供体NOC-18联合使用可增强OSC细胞的抗肿瘤作用。单用5-FU或硝酸甘油（NTG）处理裸鼠背部皮下组织的异种肿瘤移植物的生长速率均有中度降低，5-FU与NTG联合处理的肿瘤移植物生长速率明显降低。5-FU和NTG联合使用可显著降低HIF-1α蛋白及其靶基因产物VEGF和GLUT-1的表达水平。此外，与NTG联合使用可提高OSC患者放化疗的临床效果。这些结果提示，NO供体联合化疗药物治疗OSC是相当有效的。

We investigated the effect of the nitric oxide (NO) donor on the antitumor activity of chemotherapeutic drugs to oral squamous cell carcinoma (OSC) cells. The antitumor effect of 5-FU to OSC cells was enhanced by the combination with NO donor, NOC-18 under both normoxic and hypoxic conditions. The growth rates of tumor xenografts implanted into the subcutaneous tissues of back of the nude mice were moderately attenuated by the treatment with 5-FU or nitroglycerin (NTG) alone and the rates were strongly reduced by the combination of 5-FU and NTG. The expression levels of HIF-1α protein and its target gene products (VEGF and GLUT-1) were significantly decreased by the combination with 5-FU and NTG. Furthermore, clinical effects of chemoradiotherapy in patients with OSC were enhanced by the combination with NTG. These results suggest that the combination with NO donor and chemotherapeutic drugs is considerable in the treatment of OSC.