目的研究没食子酸抑制小鼠模型中人神经母细胞瘤增殖的作用以及对化疗药物的协同作用。方法建立人神经母细胞瘤SK-N-SH细胞株免疫活性C57BL/6j小鼠移植瘤模型,随机分配成4组,每组10只:①PBS荷瘤对照组,按PBS0.5ml/只,腹腔注射,作为阴性对照;②没食子酸组,按250mg/kg,1次/2d给药,连续2周;③环磷酰胺组,按75mg/kg给药,每周2次,连续2周,作为阳性对照;④没食子酸+环磷酰胺组,没食子酸在环磷酰胺给药前24h给药,没食子酸与环磷酰胺独立给药,剂量和时间同前。药物均9:00腹腔注射给药,每周监测相对肿瘤体积(RTV),治疗时间共2周,次日处死小鼠,称体质量和瘤质量(Wt)、计算抑瘤率(IR),BrdU标记检测移植瘤细胞增殖。结果没食子酸组、环磷酰胺组、没食子酸+环磷酰胺组在2周的移植瘤瘤质量分别为(4559.0±677.7)、(2117.0±749.6)、(637.7±319.6)mg,平均抑瘤率分别为36.94%、70.72%、91.18%,与PBS组比较差异有显著性(P〈0.01),没食子酸+环磷酰胺组瘤质量与环磷酰胺组比较差异有显著性(P〈0.01)。各给药组肿瘤增殖指数分别为0.1229±0.0219、0.1076±0.0156、0.0413±0.0130,与PBS组肿瘤增殖指数(0.2308±0.0759)比较差异有显著性(P〈0.01),同时没食子酸+环磷酰胺组与没食子酸组或环磷酰胺组比较差异有显著性(P〈0.01)。结论没食子酸具有抑制人神经母细胞移植瘤增殖、协同环磷酰胺抗肿瘤生长的作用。
Objective To study inhibitory effects of gallic acid(GA) on human neuroblastoma xenograft model,and its synergistic effect with chemotherapy.Methods A total of 40 3-week-old immuno-competent C57BL/6j mice were transplanted with SK-N-SH cells to established xenograft model,and then randomly divided into 4 groups,10 of each,PBS control group(0.5 ml PBS,i.p,as a negative control),GA group(250 mg/kg,i.p.,every other day,for 2 continuous weeks),cyclophosphamide(CP) group(75 mg/kg,i.p.,twice a week,for 2 weeks,as a positive control),and CP plus GA group(GA and CP were independently administered with same dose and time as above).The relative tumor volume(RTV) was monitored weekly with growth curves.The average weight of the imsplanted tumors and the tumor inhibitory rate(IR) were tested at 21st day after transplantation.Tumor cell proliferation was detected by bromouracil deoxyriboside labeling(BrdU).Results The average weight of the transplanted tumors in the GA,CP,and CP plus GA groups were 4 559.0±677.7,2 117.0±749.6,and 637.7±319.6 mg respectively,and the average IR were 36.94%,70.72%,and 91.18%,respectively.Significant difference was observed in average tumor weight in these 3 groups compareel with the PBS group(P0.01),and between the CP plus GA group and the CP group(P0.01).Tumor proliferation index(LI) were 0.122 9±0.021 9,0.107 6±0.015 6,and 0.041 3±0.013 0,respectively in the tumor tissues of GA,CP,and CP plus GA groups,significant higher than that of the PBS group(0.230 8±0.075 9,P0.01).LI of the mice with CP plus GA treatment was significantly smaller than that treated by CP or GA(P0.01).Conclusion GA can inhibit tumor proliferation,and exert synergistic effect with CP to suppress the growth of human neuroblastoma xenograft.