Alphastatin多肽联合紫杉醇对裸鼠卵巢癌的治疗作用  

Therapeutic effect of alphastatin peptide and paclitaxel on ovarian cancer in nude mice

作　　者：尉春艳[1] 弥少茹 常健 张熙[3] WEI Chunyan;MI Shaoru;CHANG Jian;ZHANG Xi(Department of Obstetrics and Gynecology,Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Department of Obstetrics and Gynecology,Chengcheng County Hospital;Department of Neurosurgery,Second Affiliated Hospital of Xi’an Jiaotong University)

机构地区：[1]西安交通大学第二附属医院妇产科,西安710004 [2]陕西省澄城县医院妇产科 [3]西安交通大学第二附属医院神经外科

出　　处：《山西医科大学学报》2018年第7期809-812,共4页Journal of Shanxi Medical University

基　　金：陕西省自然科学基础研究计划项目(2014JM2-8181)

摘　　要：目的探讨血管生成抑制肽alphastatin联合紫杉醇对卵巢癌的治疗作用。方法构建卵巢癌裸鼠模型,将裸鼠分为对照组、alphastatin组、紫杉醇组、紫杉醇和alphastatin联合治疗组。alphastatin组每隔2 d腹腔注射alphastatin多肽1次,每次0.25 mg/kg,一共6次。紫杉醇组尾静脉注射紫杉醇溶液,按20 mg/kg给药,每隔2 d注射1次,共6次。联合治疗组每隔2d腹腔注射alphastatin多肽同时尾静脉注射紫杉醇溶液,剂量如前。对照组注射等体积的PBS溶液。检测各组肿瘤质量、体积、微血管密度以及VEGF,AKT和PI3K蛋白的表达。结果对照组中肿瘤的体积是(1.21±0.28)cm3,质量为(2.16±0.47)g,微血管密度是28.66±5.26;alphastatin组和紫杉醇组肿瘤的体积和质量显著降低,抑瘤率分别为37.0%和33.1%,微血管密度分别为17.53±3.54和17.13±3.33,与对照组比较差异具有统计学意义(P<0.05);联合治疗组与对照组比较,肿瘤的体积、质量和微血管密度进一步减少,抑瘤率达到了68.1%,微血管密度为10.69±2.24,与对照组、alphastatin组或紫杉醇组比较,差异均有统计学意义(P<0.05)。紫杉醇或alphastatin均能抑制VEGF,AKT和PI3K蛋白的表达,但是联合紫杉醇和alphastatin多肽后VEGF、AKT和PI3K蛋白的表达进一步降低。结论 alphastatin多肽联合紫杉醇能够通过抑制VEGF/AKT/PI3K信号通路,抑制肿瘤内部血管生成,达到更好的治疗效果。Objective To investigate the therapeutic effect of alphastatin peptide and paclitaxelon on ovarian cancer in nude mice.Methods The ovarian cancer models in nude mouse were established and divided into four groups:control group,alphastatin group,paclitaxel group,and paclitaxel+alphastatin group.In alphastatin group,mice were injected intraperitoneally with 0.25 mg/kg alphastatin peptide every 2 d for 6 times.In paclitaxel group,mice were injected with 20 mg/kg paclitaxel in tail vein every 2 d for 6 times in total.In combination group,mice were intraperitoneally injected with alphastatin peptide and injected with paclitaxel in tail vein every 2 d.The mice in control group were injected with equal volume of PBS solution.The weight,volume and microvascular density were tested and the expression of VEGF,AKT and PI3K was also detected.Results In control group,the mean tumor volume was(1.21±0.28)cm 3,mean tumor weight was(2.16±0.47)g,and mean number of microvascular density(MVD)was 28.66±5.26.In alphastatin group and paclitaxelthe group,the tumor inhibition rate was 37.0%and 33.1%,the mean number of MVD was 17.53±3.54 and 17.13±3.33,respectively.The tumor weight,volume and MVD were significantly lower in alphastatin group and paclitaxelthe group than in control group(P<0.05).In combination group,the tumor weight,volume and MVD were significantly lower than those in the other three groups(P<0.05).The tumor inhibition rate was 68.1%in combination group,and the mean number of MVD was 10.69±2.24.The expression of VEGF,AKT and PI3K was lower in paclitaxel group and alphastatin group than in control group,and the lowest in combination group.Conclusion Combination of paclitaxel and alphastatin is benefit to treat ovarian cancer by inhibiting VEGF/AKT/PI3K pathway and angiogenesis.

关 键 词：卵巢癌 紫杉醇 alphastatin多肽 化疗敏感性 

分 类 号：R737.31[医药卫生—肿瘤]