维生素D_(3)通过抑制血小板活化影响裸鼠乳腺癌移植瘤的生长  

Effect of vitamin D_(3)on growth of breast cancer xenografts in nude mice by inhibiting platelet activation

作　　者：王旭颖 荆明箴 付荣[1] 余谨[1] 杨茹 WANG Xuying;JING Mingzhen;FU Rong;YU Jin;YANG Ru(Department of Clinical Laboratory,Wuhan Blood Center,Wuhan 430030,Hubei Province,China;Laboratory of Blood Transfusion,Wuhan Blood Center,Wuhan 430030,Hubei Province,China)

机构地区：[1]武汉血液中心检验科,湖北武汉430030 [2]武汉血液中心输血研究室,湖北武汉430030

出　　处：《肿瘤》2021年第7期451-459,共9页Tumor

基　　金：国家自然科学基金青年科学基金(31600111)。

摘　　要：目的:观察维生素D_(3)对裸鼠乳腺癌移植瘤生长的影响,并探讨其对荷瘤小鼠血小板活化的影响。方法:将18只BALB/c裸鼠随机分为正常组、模型组和维生素D_(3)治疗组,每组6个小鼠;模型组和维生素D_(3)组小鼠首先通过皮下注射乳腺癌4T1细胞建立移植瘤模型。10d后维生素D_(3)治疗组小鼠开始腹腔注射维生素D_(3)(0.05μg/d)连续干预10d;测量肿瘤长、短径并绘制肿瘤生长曲线。收集裸鼠外周血及肿瘤组织,采用HE染色观察肿瘤组织病理变化。分离外周血血小板,采用FCM法检测血小板活化标志物CD61和CD62p以及晚期糖基化终末产物受体(receptor for advanced glycation end product,RAGE)的表达水平,酶联免疫吸附测定(enzyme-linked immuno sorbent assay,ELISA)法检测外周血中血管性血友病因子(vonwillebrandfactor,v WF)的浓度。结果:在模型组和维生素D_(3)治疗组裸鼠中建立乳腺癌4T1细胞移植瘤模型。与模型组相比,维生素D_(3)治疗组移植瘤的体积明显减少(P<0.05),肿瘤质量明显减轻(P<0.05),肿瘤组织中血管生成减少,出现肿瘤细胞死亡。与正常组相比,模型组小鼠血小板中CD61、CD62p和RAGE阳性表达率以及v WF浓度均明显升高(P均<0.05);与模型组相比,维生素D_(3)治疗组小鼠血小板中CD61、CD62p和RAGE阳性表达率,以及v WF浓度均明显降低(P均<0.05)。结论:维生素D_(3)可抑制裸鼠乳腺癌移植瘤生长,其抗肿瘤作用可能与抑制血小板活化聚集有关。Objective:To investigate the effect of vitamin D_(3)on the growth of breast cancer xenografts in nude mice,and explore its effect on platelet activation in mice bearing tumor.Methods:18 BALB/c nude mice were randomly divided into 3 groups:normal group,model group and vitamin D_(3)treatment group with 6 mice in each group.Breast cancer cells 4T1 were subcutaneously injected into mice in model and vitamin D_(3)treatment groups.After 10 d,vitamin D_(3)treatment group was injected with vitamin D_(3)(0.05μg/d)for 10 d.The length and short diameter of tumors were measured and the growth curve of tumor was drawn.Peripheral blood and tumor tissues of nude mice were collected and the pathological changes of tumor tissues were examined by HE staining.Platelet activation markers CD61,CD62P and receptor for advanced glycation end products(RAGE)were analyzed by flow cytometry(FCM)method.Von willebrand factor(v WF)concentration in peripheral blood was measured by enzyme-linked immuno sorbent assay(ELISA).Results:The breast cancer 4T1 cell xenograft model was established in model gruop and vitamin D_(3)treatment group.Compared with the model group,the tumor volume and weight in vitamin D_(3)treatment group were significantly reduced(both P<0.05),angiogenesis in tumor tissue was reduced,and cancer cell death occurred.Compared with the normal group,the positive expression rates of CD61,CD62p and RAGE and the concentration of v WF in the model group were significantly increased(all P<0.05).Compared with the model group,the positive expression rates of CD61,CD62p and RAGE and the concentration of v WF in the vitamin D_(3)treatment group were significantly decreased(all P<0.05).Conclusion:Vitamin D_(3)can inhibit the growth of breast cancer xenografts in nude mice,and its anti-tumor effect may be related to the inhibition of platelet activation and aggregation.

关 键 词：乳腺肿瘤 维生素D 血小板活化 模型 动物 

分 类 号：R73[医药卫生—肿瘤]