阿苯达唑抑制胶质瘤裸鼠模型肿瘤生长

Albendazole inhibits tumor growth in nude mice model of glioma

目的探讨阿苯达唑(ABZ)对胶质瘤裸鼠模型肿瘤生长的影响。方法将术中获取的胶质母细胞组织消化为单细胞悬液用无血清干细胞培养基进行培养胶质母细胞瘤干细胞(GSC),用含10%胎牛血清的DMEM培养基培养胶质瘤细胞系U87、U251、U172,以25、50、100、200 ng/ml的终浓度ABZ作用细胞,采用MTT法检测细胞增殖。右侧腋窝皮下注射0.2 ml(5×10^6个细胞)GSC及U87细胞悬液构建胶质瘤裸鼠模型,将30只胶质瘤裸鼠模型随机分为6组,GSC和U87细胞移植各3组,每种移植瘤模型均分为模型组(腹腔注射等体积DMSO)、低剂量ABZ组(腹腔注射ABZ,50 mg/kg)、高剂量ABZ组(腹腔注射ABZ,100 mg/kg)。定时测量肿瘤长径与短径,计算肿瘤体积;PCR法和免疫印迹法检测裸鼠肿瘤组织血管内皮生长因子(VEGF)mRNA和蛋白表达水平。结果ABZ对GSC、U87、U251和A172细胞生长均具有明显抑制效果(P<0.05),而且抑制效果具有浓度依赖性(P<0.05),浓度>50 ng/ml抑制效果较好。腹腔注射ABZ后,高剂量和低剂量ABZ组移植瘤体积增长较对照组均明显减慢(P<0.05)。高剂量ABZ组和低剂量ABZ组肿瘤VEGF mRNA和蛋白表达水平较对照组均明显降低(P<0.05)。结论ABZ可以抑制胶质瘤裸鼠模型肿瘤生长,可能与抑制肿瘤细胞增殖和血管生成有关。

Objective To investigate the effect of albendazole(ABZ)on tumor growth in nude mice model of glioma.Methods The glioblastoma tissue obtained during the operation was digested into single cell suspension and cultured in serum-free glioblastoma stem cell(GSC)medium.The glioma cell lines U87,U251,and U172 were cultured in DMEM medium containing 10%fetal bovine serum.All the cultured cells were treated with ABZ with a final concentration of 25,50,100,200 ng/ml,respectively.The proliferation rates of cultured cells were detected by MTT assay.The nude mice model of glioma was established using subcutaneous injection of 0.2 ml(5×10^6 cells)GSC and U87 cells suspension into the right armpit.Thirty nude mice models were randomly divided into 6 groups,3 groups of GSC and 3 groups of U87.Each transplantation model was divided into model group(intraabdominal injection of equal volume DMSO),low dose ABZ group(intraabdominal injection of ABZ,50 mg/kg)and high dose ABZ group(intraabdominal injection of ABZ,100 mg/kg).The long diameter and short diameter of the tumor were measured regularly to calculate the tumor volume,and the mRNA and protein expressions of vascular endothelial growth factor(VEGF)in tumor tissues of nude mice were detected by PCR and immunoblotting,respectively.Results ABZ had a significant inhibitory effect on the growth of GSC,U87,U251 and A172 cells in a concentration-dependent manner,and the inhibitory effect was better when the concentration was more than 50 ng/ml.After intraabdominal injection of ABZ,the growth of tumor volume in high dose and low dose ABZ group was significantly slower than that in control group(P<0.05).The expression levels of VEGF mRNA and protein in high dose and low dose ABZ groups were significantly lower than those in control group(P<0.05).Conclusion ABZ can inhibit the growth of glioma in nude mice,which may be related to the inhibition of tumor cell proliferation and angiogenesis of tumor.