靶向巨噬细胞移动抑制因子的siRNA对小鼠大肠癌肝转移的影响  

Effects of macrophage migration inhibitory factor siRNA on hepatic metastasis of mouse colonic cancer

作　　者：杨荣娇[1] 王丽京[2] 臧林泉[2] 王亚敏[1] 吴礼浩[1] 舒阳春[1] 何兴祥[1] 

机构地区：[1]广东药学院附属第一医院消化科,广州510080 [2]广东药学院基础医学院

出　　处：《中华实验外科杂志》2011年第9期1495-1497,共3页Chinese Journal of Experimental Surgery

基　　金：广东省高等学校高层次人才项目[粤教师函（2010）79号];广东省科技计划资助项目（2008A030201001）;广东省自然科学基金资助项目（9251065005000001）

摘　　要：目的探讨靶向巨噬细胞移动抑制因子（MIF）的小干扰RNA（siRNA）对BALB／C小鼠大肠癌肝转移的影响及其可能的机制。方法盲肠造疝原位接种瘤块法建立BALB／C小鼠大肠癌肝转移模型。将成功建模的小鼠随机分为3组。分别每周2次肿瘤原位注射相同体积的靶向MIF的siRNA（MIFsiRNA，0．15ng／kg）、非特异性siRNA（NS-siRNA，0．15ng／kg）及生理盐水（Ns，0．15ng／kg），治疗4周。治疗结束3d后，处死小鼠。肝脏连续切片，苏木素-伊红（HE）染色观察各组大肠癌肝转移；酶联免疫吸附试验（ELISA）检测血清MIF及血管内皮生长因子（VEGF）浓度；免疫组织化学染色检测肝转移灶微血管密度（MVD）。结果MIFsiRNA组、NS-siRNAR组及NS组的大肠癌肝转移率分别为10％、60％与70％（X2=8．30，P〈0．05），小鼠血清MIF分别为（20±4）、（72±8）与（78±7）ng/L（P〈0．05）；小鼠血清VEGF分别为（20±4）、（77±9）与（77±10）ng／L（P〈0．05）；肝转移灶的MVD分别为19±3、29±6与35±7（P〈0．05）。结论靶向MIF的siRNA降低了小鼠大肠癌肝转移的发生率，其机制可能是靶向MIF的siRNA抑制了MIF表达，下调VEGF的表达，减少了MVD。Objective To investigate the effects of macrophage migration inhibitory factor （MIF） small interfering RNA （siRNA） , a siRNA targeting MIF on hepatic metastasis in a BALB/C mouse model of colonic cancer. Methods Orthotopic transplantation of fresh colorectal cancer tumor fragments into hernial sac of cecum was used in a BALB/C mouse model of coloreetal cancer. Thirty mouse models were divided randomly into three groups and treated respectively with MIF siRNA （0. 15 ng/kg）, NC-MIF siRNA and normal saline （NS） twice a week, intratumorally. After 4th week, mice were sacrificed and the total livers were made into serial slices to detect the occurrence of hepatic metastasis. Enzyme linked immu- nosorbent assay （ELISA） was used to test the serum MIF and vascular endothelial growth factor （YEGF） concentrations. Immunohistochemical staining of CD31 was used for comparing microvessel density of the tumor tissue. Results Compared with NC-MIF siRNA and NS groups, MIF siRNA decreased the occurrence of hepatic metastasis （ 10%, 60% and 70%, respectlvely;χ2 = 8. 30 ,P 〈0. 05 ）. Also MIF siRNA decreased serum MIF levels [ （20 ±4） , （72 ±8） and （78±7） ng/L, respectively,P 〈0.05] and VEGF levels [ （ 20 ± 4 ）, （77 ±9 ）, （77 ± 10） ng/L, respectively, P 〈 0. 05 ]. The MVD of hepatic tumor tissues in MIF-siRNA, NC-MIF siRNA and NS groups was 19 ±3, 29 ±6 and 35 ±7, respectively （P 〈0. 05）. Conclusion MIF siRNA reduced the occurrence of hepatic metastasis, possibly by a mechanism of MIF siRNA inhibiting the expression of MIF, down-regulating the expression of VEGF and reducing MVD.

关 键 词：大肠癌 MIF SIRNA 转移 

分 类 号：R735.34[医药卫生—肿瘤]