白藜芦醇对裸鼠胶质瘤模型肿瘤生长的抑制作用

Resveratrol inhibits tumor growth in nude mice model of glioma

目的探讨白藜芦醇(RES)不同途径给药对裸鼠胶质瘤模型肿瘤生长的抑制效果。方法取80只雄性无胸腺裸鼠(BALB/c-nu;21~27日龄,体重10~12g),采用U87细胞建立人裸鼠脑胶质瘤原位移植模型,采用随机数字表法分为RES干预组(造模后10d,开始给药,1次/d,40mg/kg)和溶剂对照组(造模后10d,开始给药,1次/d,10mg/kg;溶剂为0.5%羧甲基纤维素钠),根据给药途径,RES干预组又分为RES灌胃组和RES经鼻组,溶剂对照组又分为溶剂灌胃组和溶剂经鼻组,每组20只。经鼻给药采用经鼻滴入法。采用Kaplan-Meier法分析生存曲线;造模后14、21、28、35d测定肿瘤体积;采用CD31标记胶质瘤血管内皮细胞并计算微血管密度(MVD),采用免疫组化方法检测胶质瘤血管内皮生长因子(VEGF)以及Ki-67表达,采用TUNEL法检测胶质瘤细胞凋亡。结果与溶剂对照组相比,RES干预组裸鼠生存时间明显延长(P<0.05),造模后28、35d肿瘤体积明显缩小(P<0.05),肿瘤组织MVD明显减小(P<0.05),肿瘤组织VEGF和Ki-67表达水平明显降低(P<0.05),肿瘤细胞凋亡率明显增加(P<0.05),而且,RES经鼻给药较灌胃给药作用更明显(P<0.05)。结论RES可有效抑制裸鼠胶质瘤模型肿瘤生长,机制可能与抑制肿瘤血管生成和促进肿瘤细胞凋亡有关。与灌胃给药相比,经鼻给药肿瘤抑制效果更好。

Objective To investigate the effect of resveratrol (RES) on tumor growth in nude mice model of glioma.Methods Eighty nude mice models of glioma were established by injection of U87 cells into the cerebral tissues,then these nude mice were randomly divided into RES intervention group (administration 10 days after injection of U87 cells,40 mg/kg) and solvent control group (administration 10 days after injection of U87 cells,once a day,10 mg/kg;the solvent was 0.5% sodium carboxymethyl cellulose). According to the route of administration,the RES intervention group was then divided into RES intragastric group and RES transnasal group,and the solvent control group was divided into solvent intragastric group and solvent transnasal group,with 20 mice in each group. The survival time was analyzed by Kaplan-Meier method,the tumor volume was measured at 14,21,28 and 35 days after injection of U87 cells,the microvessel density (MVD) was calculated by labeling the vascular endothelial cells with CD31,the expressions of vascular endothelial growth factor (VEGF) and Ki-67 were detcted by immunohistochemical staining,and the apoptosis of glioma cells was detected by TUNEL method.Results Compared with the solvent control group,the survival time of nude mice was significantly prolonged (P<0.05),the tumor volume was significantly reduced (P<0.05),the MVD of tumor tissue was significantly decreased (P<0.05), the expressions of VEGF and Ki-67 in tumor tissue was significantly decreased (P<0.05),and the apoptosis rate of tumor cells was significantly increased in RES intervention group (P<0.05).Moreover,the tumor inhibitory effect of RES by transnasal administration was significantly better than RES by intragastric administration (P<0.05).Conclusion RES can effectively inhibit the tumor growth in nude mice model of glioma,which may be related to the inhibition of tumor angiogenesis and the promotion of tumor cell apoptosis. Compared with the intragastric administration,transnasal administration of RES has better tumor inhibitory effect.