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机构地区:[1]新乡医学院药学院,河南新乡453003 [2]新乡医学院基础医学院,河南新乡453003
出 处:《广东医学》2015年第11期1638-1641,共4页Guangdong Medical Journal
基 金:国家自然科学基金资助项目(编号:81072552);新乡医学院培育基金项目(编号:2014QN130)
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。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 physio-logical 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 in-jection 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 p 53 was measured by immunohistochemistry and real -time fluo-rescence 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 p 53 protein and mRNA (P〈0.01) were observed, which were close to that of the cyclophosphamide group .Conclusion GLA-γ-CD can in-duce apoptosis and inhibit growth of tumor cells , which may be associated with regulating the expression of mutant p 53, with little cytotoxicity .
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