乙酰肝素酶反义寡核苷酸对裸鼠人食管鳞癌移植瘤的抑制作用  

Inhibitory effect of heparanase antisense oligodeoxynucleotide on growth and angiogenesis of xenograft esophageal squamous cell carcinoma in nude mice

作　　者：朱辉[1] 王士杰[1] 单保恩[1] 王小玲[1] 孟宪利[1] 何明[1] 

机构地区：[1]河北医科大学第四医院,河北石家庄050011

出　　处：《山东医药》2008年第21期17-19,共3页Shandong Medical Journal

基　　金：河北省科技支撑计划项目(0727611013);河北省普通高等学校强势特色学科建设项目(冀教高2005-52)

摘　　要：目的研究乙酰肝素酶(Hpa)抑制剂反义脱氧寡核苷酸(ASODN)对食管癌裸鼠移植瘤的体内抑瘤作用。方法采用低分化食管鳞癌细胞TE-13接种裸鼠,构建食管癌皮下侵袭模型,随机分为1 mg/kg ASODN组(A组)、2 mg/kg ASODN组(B组)和生理盐水(NS,2 ml/kg)对照组(C组),每组5只,分别在肿瘤接种区皮下注射相应剂量的ASODN和NS。观察肿瘤体积和肿瘤微血管密度(MVD),采用RT-PCR和免疫组化染色检测移植瘤中Hpa的表达。结果接种后第6天,所有裸鼠在接种部位均长出肿瘤。接种后第21天,A、B组肿瘤体积较C组明显缩小(P<0.01),A、B组抑瘤率分别为50.27%和49.67%。A、B组MVD较C组明显降低(P<0.01)。A、B、C组Hpa mRNA阳性表达分别为0.43±0.01、0.45±0.12、1.33±0.05,Hpa蛋白阳性表达分别为45.60±4.57、43.40±7.80、121.20±11.90。A、B组Hpa mRNA、蛋白表达均较C组降低(P<0.01)。结论应用ASODN可以抑制肿瘤生长,其作用机制可能在于抑制肿瘤Hpa mRNA、蛋白合成,从而抑制肿瘤血管新生。2 mg/kg与1 mg/kg HpaASODN比较,未能显示更强的抑瘤效果。Objective To observe inhibitory effect of Hpa ASODN on growth and angiogenesis of esophageal squamous cell carcinoma （ESCC） xenograft tumor in nude mice. Methods ESCC cell line TE-13 was injected subcutaneously in nude mice to establish the ESCC subcutaneous invasive model. The nude mice were randomized into 1 mg/kg ASODN （group A） ,2 mg,/kg ASODN（ group B）and sterile saline control group（ group C）. Each group contained 5 mice. Tumor volume and micro vessel density （MVD） were observed. Hpa expression was detected by RT-PCR and immunohistochemistry. Results In the 6 th day after injection,all mice had palpable tumors. In the 21 st day after injection,the tumor volume in group A and B was less than that in group C （P〈0.01）. The ratios of suppress in group A and B were 50.27% and 49. 67%. The MVD was significantly less in group A and B than that in group C （ P 〈 0. 01 ）. Hpa mRNA expression in group A,B and C was 0. 43 ±0. 01,0. 45 ±0. 12 and 1.33 ±0. 05 respectively. Hpa protein expression in group A,B and C was 45. 60 ±4. 57,43.40 ±7. 80 and 121.20 ± 11.90 respectively. Data showed that Hpa gene and protein expression in group A and B was less than that in group C （ P 〈 0. 01 ）. Conclusions ASODN administration could reduce the tumor growth,angiogenesis and Hpa expression in vivo. 2 mg/kg Hpa ASODN showed no better result than 1 mg/kg Hpa ASODN.

关 键 词：食管肿瘤 乙酰肝素酶 反义寡核苷酸 裸鼠 

分 类 号：R735.1[医药卫生—肿瘤]