【摘要】 目的探讨蓝萼甲素γ-环糊精包合物(GLA-γ-CD)对荷瘤小鼠S180移植瘤生长及凋亡的影响。方法制备小鼠S180皮下移植瘤模型,随机分为5组,每组10只。对照组给予生理盐水,环磷酰胺组给予环磷酰胺10 mg/kg,GLA-γ-CD高、中、低剂量组分别给予GLA-γ-CD 80、40、20 mg/kg,均腹腔注射给药12 d,观察抑瘤作用,TUNEL法检测细胞凋亡,免疫组化法及实时荧光定量PCR法分别检测突变型p53蛋白及mRNA的表达。结果与对照组比较,GLA-γ-CD各剂量组的瘤重均明显降低(P<0.01,P<0.05),其中GLA-γ-CD高剂量组抑瘤率达57.26%,肿瘤细胞凋亡指数明显提高(P<0.01),突变型p53蛋白及mRNA表达显著降低(P<0.05),且与环磷酰胺组作用相当。结论 GLA-γ-CD能明显抑制S180肿瘤生长,其机制可能与减少突变型p53的表达,从而诱导细胞凋亡有关;并且GLA-γ-CD在发挥抗肿瘤同时毒性作用不大,具有较好的开发前景。更多还原

【Abstract】 Objective To investigate the effects of glaucocalyxin A included by γ- cyclodextrin( GLA- γ-CD) on transplanted S180 tumor growth and apoptosis. Methods The transplanted S180 tumor models were established by implanting S180 cells into mice. The mice were randomly divided into 5 groups( n = 10),control group( given with physiological saline),cyclophosphamide group( given with 10 mg / kg cyclophosphamide),GLA- γ- CD high,middle and low dose groups( given with 80,40,and 20 mg / kg GLA- γ- CD,respectively). All drugs were given as intraperitoneal injection every day for 12 days. The effect of GLA- γ- CD on tumor growth was observed. Cell apoptosis was determined by TUNEL. The protein and mRNA expression of mutant p53 was measured by immunohistochemistry and real- time fluorescence quantitative RT- PCR,respectively. Results Compared with control group,the tumor weight in each GLA-γ- CD group was significantly reduced( P < 0. 01,P < 0. 05). The tumor inhibition rate against S180 of GLA- γ- CD high dose group was 57. 26%,and increased apoptosis index and down- regulation of mutant p53 protein and mRNA( P < 0. 01) were observed,which were close to that of the cyclophosphamide group. Conclusion GLA- γ- CD can induce apoptosis and inhibit growth of tumor cells,which may be associated with regulating the expression of mutant p53,with little cytotoxicity.更多还原