西地那非对荷S180小鼠抗肿瘤作用的实验

Anti-tumor Effect of Sildenafil on S180 Sarcoma

目的观察西地那非抗肿瘤及化疗增效的作用,探讨可能的机制。方法建立S180小鼠模型。西地那非分低、中、高剂量单独给药或联合化疗。比较抑瘤率;给药第6天流式细胞仪检测中剂量西地那非组、对照组肿瘤细胞凋亡及细胞周期分布,ELISA法检测肿瘤细胞内血管内皮生长因子(VEGF)、p53、环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)的水平。结果联合化疗组抑瘤率高于西地那非组,西地那非组又高于对照组;中剂量西地那非组p53、VEGF、细胞周期分布与对照组相比无差异,cGMP、细胞凋亡率高于对照组,cAMP低于对照组。结论西地那非有一定的抗肿瘤和化疗增效作用;这种作用与诱导肿瘤细胞的凋亡相关,与细胞周期阻滞、VEGF、p53的变化无关。

Objective To observe the anti-tumor effect and the enhancement effect on chemotherapy of sildenafil and its possible mechanism. Methods Mice with S180 sarcoma were divided into groups randomly. The treated groups were administered low[30 mg/（kg· d） ], moderate[60 mg/（kg· d）] and high[ 100 mg/（kg· d）]dose sildenafil separately or combined with cyclophophamide （CTX）. The tumor-inhibitory rate was counted. Apoptosis and cell cycle of tumor cells in mice treated with medium dose sildenafil were detected with fluorescence microscopy at six day. The level of VEGF, p53, cAMP, cGMP of tumor cell in mice treated with medium dose sildenafil were detected by ELISA at six day. Results The tumor-inhibitory rate of co-chemotherapy group was higher than sildenafil groups, and both of them were higher than blank control group. The level of VEGF, p53 and cell cycle in tumor cell of sildenafil groups were no difference with blank control group, but the level of cGMP and apoptosis rate were higher than blank control group, the level of cAMP decreased in sildenafil group. Conclusion Sildenafil had the anti-tumor effect and the enhancement effect of chemotherapy. The mechanism was that it may induce tumor cell apoptosis,and was irrelevant with the change of cell cycle, VEGF and p53.