1,25二羟基维生素D_3联合5-氟尿嘧啶对人食管癌Eca-109细胞移植瘤的影响  

Effect of 1,25-dihydroxyvitamin D_3 combined with 5-fluorouracil on IGFBP-3 expression in human esophageal carcinoma 109 cell xenograft in nude mice

作　　者：李钢[1] 蒋迎九[1] 吴庆琛[1] 李强[1] 余敏[2] 汤为学[3] 

机构地区：[1]重庆医科大学附属第一医院胸心外科,重庆400016 [2]重庆市北碚区中医院,重庆400711 [3]重庆市神经病学重点实验室,重庆400016

出　　处：《南方医科大学学报》2012年第4期575-579,共5页Journal of Southern Medical University

基　　金：重庆市渝中区科技计划项目(2010126)

摘　　要：目的探讨1,25二羟基维生素D3、5-氟尿嘧啶单独或联合作用对人食管癌Eca-109细胞裸鼠移植瘤胰岛素生长因子结合蛋白-3(IGFBP-3)的影响。方法体外培养人食管癌Eca-109细胞,BALB/c裸小鼠皮下接种荷瘤后随机分为对照组(A)、1,25二羟基维生素D3组(B)、5-氟尿嘧啶组(C)、联合用药组(D),2.5μg/kg 1,25二羟基维生素D3、25 mg/kg 5-氟尿嘧啶单独或联合腹腔注射,对照组用等体积生理盐水腹腔注射,观察瘤体生长情况,运用免疫组织化学方法检测移植瘤组织中IGFBP-3蛋白表达,全自动生化分析仪检测血清钙离子水平、Von kossa染色观察肾脏钙沉积情况。结果与A组比较,B、C、D组移植瘤生长缓慢,体积较小,IGFBP-3阳性蛋白染色较深,且表达量较多(P<0.05);而D组较B、C组移植瘤IGFBP-3蛋白表达显著升高(P<0.05)。B、C、D组血清钙离子水平较A组稍有升高,但肾脏组织切片Von kossa染色未见钙沉积。结论 1,25二羟基维生素D3、5-氟尿嘧啶均能抑制移植瘤生长,且联合用药效果更为显著,可能与上调移植瘤组织IGFBP-3蛋白表达有关。肾脏Von kossa染色未见钙沉积。Objective To investigate the effect of 1,25-dihydroxyvitamin D3 and 5-eluorouracil,either alone or in combination,on the expression of IGFBP-3 in human esophageal carcinoma 109 cell xenograft in nude mice.Methods In vitro cultured esophageal carcinoma Eca-109 cells were inoculated subcutaneously in BALB/c mice.The tumor-bearing mice were randomly devided into control group（A）,1,25-dihydroxyvitamin D3 group（B）,5-fluorouracil group（C）,and 1,25-dihydroxyvitamin D3 plus 5-fluorouracil group（D）.1,25-dihydroxyvitamin D3 and 5-fluorouracil were administered at the doses of 2.5 μg/kg and 25 mg/kg via intraperitoneal injections,respectively,and the mice in the control group received salinel injection only.The tumor growth was observed and the expression of IGFBP-3 in the tumor xenograft was detected using immunohistochemistry.An automatic biochemistry analyzer was used to determine serum calcium levels,and Von Kossa staining was utilized for observation of calcium deposition in the kidneys.Results Compared with that in group A,the xenograft in groups B,C,and D all showed a lowered growth rate with a smaller tumor volume,and presented with stronger IGFBP-3 positivity and significantly higher levels of IGFBP-3 protein expression（P0.05）.In group D,the protein expression of IGFBP-3 was significantly increased compared with that in groups B and C（P0.05）.Compared with that in group A,serum calcium level was slightly increased in groups B,C,and D,,but no obvious calcium deposition was found in the kidney tissue sections.Conclusion Both 1,25-dihydroxyvitamin D3 and 5-fluorouracil can inhibit the growth of the tumor xenograft in nude mice,and their combination is more effective.This effect is probably associated with increased protein expression of IGFBP-3 in the xenograft tumor.No calcium deposition occurs in the kidney tissue of the tumor-beairng mice.

关 键 词：食管癌 1 25二羟基维生素D3 5-氟尿嘧啶 胰岛素生长因子结合蛋白-3 钙沉积 

分 类 号：R735.1[医药卫生—肿瘤]