SKI-Ⅱ联合顺铂对人胃癌裸鼠移植瘤抑制作用及其机制探讨  

Inhibitory action of SKI-Ⅱ double DDP on human gastric cancer and its possible mechanisms in a nude mice transplanted tumors model

作　　者：王云[1] 黄广清[2] 苗怡然[1] 单海霞[2] 蔡红星 朱正秋[2] 

机构地区：[1]徐州医学院研究生学院,江苏徐州221002 [2]徐州医学院附属医院肿瘤科,江苏徐州221002 [3]盐城卫生职业学校,江苏盐城224006

出　　处：《中华肿瘤防治杂志》2013年第21期1643-1648,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：江苏省卫生厅2010年度医学科研项目(Z201016);江苏省"六大人才高峰"第七批次项目(032)

摘　　要：目的:研究鞘氨醇激酶-1(sphingosine kinase-1,SphK1)在胃癌裸鼠移植瘤血管生成中的作用及其作用机制。方法:建立人胃癌SGC7901裸鼠移植瘤模型后,将荷瘤小鼠随机分为4组,分别予以腹腔注射生理盐水、SKI-Ⅱ、顺铂和SKI-Ⅱ联合顺铂干预治疗,1次/周,共3周。每隔3d测1次肿瘤大小,绘制肿瘤生长曲线,计算抑瘤率;蛋白质印迹法法检测瘤体中SphK1和VEGF的表达;免疫组化方法检测瘤体SphK1、VEGF和CD34的表达情况及计算瘤体内瘤体微血管密度(microvessel densitv,MVD)。结果:与生理盐水组相比,3组治疗组均有抑制肿瘤生长作用,SKI-Ⅱ组和顺铂组抑瘤率分别为(48.69±1.39)%和(75.24±1.19)%;其中以SKI-Ⅱ联合顺铂组抑瘤作用最为明显,抑瘤率达(90.25±1.53)%,各组抑瘤率之间差异有统计学意义,F=1865,P<0.001。免疫组化结果示,SKI-Ⅱ和SKI-Ⅱ联合顺铂组SphK1蛋白表达分别为(45.62±7.54)%和(20.50±5.96)%,VEGF蛋白表达分别为(45.38±7.82)%和(22.25±4.74)%,瘤体内的MVD为15.12±1.55和9.38±1.92,与对照组差异有统计学意义,P<0.001。单用顺铂对SphK1表达(82.50±5.95)%)、VEGF的表达(83.25±4.40)%及瘤体内MVD(24.50±5.42)的影响差异无统计学意义,P>0.05。Pearson相关分析显示,瘤体组织SphK1与VEGF的表达呈正相关,r=0.968,P<0.001;瘤体组织MVD计数与VEGF表达呈正相关,r=0.862,P<0.001。蛋白质印迹法检测结果示,SKI-Ⅱ及SKI-Ⅱ联合顺铂组可显著下调SphK1和VEGF的表达,P<0.001,单用顺铂对SphK1和VEGF的表达差异无统计学意义,P值分别为0.083和0.165。结论:下调SphK1的表达后,可减少VEGF合成与分泌,并抑制肿瘤血管生成,可能是抑制裸鼠胃癌移植瘤生长的途径之一。OBJECTIVE：To investigate the role of SphK1 on Human gastric cancer development and angiogenesis, and explore its possible mechanisms. METHODS： Human SGC7901 carcinoma cells were inoculated into BALB/c nude mice to develop the tumor model of human gastric cancer carcinoma. The tumor-bearing nude mice were randomly divided into 4 groups ： normal saline control group, DDP group, SKI-Ⅱ group, SKI Ⅱ double DDP group. All rats were given intrap- eritoneal injection of drugs once a week for three weeks. The tumor mass volume was observed every 3 days and the inhibi- tion rate of tumor growth were also calculated. The tumor sizes were measured for tumor growth curve. All rats bodyweight change before and after treatment were observed. Western Blot was used to detect the expression of SphK1, VEGF. Immunohistoehemical staining was used to detect the expression of SphK1, VEGF and CD34 ,and MVD was coun- ted. RESULTS： Compared to the normal saline control group, all treatment groups inhibited the growth of xenografted gastric carcinoma inordinately. The inhibition of SKI- l] group and DDP group was （48.69±1.39）%, （75.24±1.19） %, respectively. The inhibition of SKI- l] combined with DDP group was quite obvious,inhibition rate for xenografts reached （90.25 ± 1.53）%. There was significant difference between each treatment group （F= 1865, P〈0. 001）. The result of immunohistochemical showed that after being treated with the SKI-l] or SKI-II double DDP, expression of SphK1 [（45.62±7.54） %,（20.50±5.96）%],VEGFff（45.38±7.82）%], （22.25±4.74）%],MVD （15.12±1.55,9.38±1.92） were decreased significantly comparing with those in controls（P〈0. 001） ,respectively. The expression of SphK1 （82.50± 5.95） % ,VEGF（83. 25±4. 40） % and MVD（24. 50±5. 42） were not different in DDP group（P〉0.05）. Pearson correla tion analysis showed that there were significant correlation between SphK1 and VEGF （r= 0. 968,P〈0. 001）, VEGF and MVD（r= 0. 862, P〈0. 001）. The re

关 键 词：胃肿瘤 磷酸鞘氨醇激酶1 血管内皮生长因子 微血管密度 裸鼠 

分 类 号：R735.2[医药卫生—肿瘤]