ISO-1对结直肠癌生长和微血管形成的影响  

Effect of ISO-1 on the growth and angiogenesis of mouse colorectal cancer xenografts

作　　者：刘成勇[1] 何兴祥[2] 陈萌[1] 黄素娴[1] 郭海波[3] 苏杭[4] 

机构地区：[1]广州医学院第二附属医院消化内科,510260 [2]广东药学院临床医学院内科教研室 [3]广州医学院第二附属医院检验科,510260 [4]广州医学院第二附属医院临床分子医学实验中心,510260

出　　处：《中华生物医学工程杂志》2007年第6期353-356,共4页Chinese Journal of Biomedical Engineering

基　　金：国家自然科学基金（30470435）;广东省自然科学基金（06022450、7101731）;广东药学院科研启动基金（2006LCY07）;广州市科学技术局科技攻关计划（2006Z3-E0201）

摘　　要：目的观察选择性巨噬细胞移动抑制因子（MIF）互变异构酶活性抑制剂ISO-1对结直肠癌生长及其微血管形成的影响，并探讨其可能机制。方法MTT法检测不同浓度ISO-1（0．01～100μmol／L）在不同时间点（24、48和72h）对CT26细胞增殖的影响。盲肠造疝原位移植瘤块术建立小鼠结直肠癌模型。将30只成功建模小鼠随机分为3组，分别每周两次腹腔注射相同体积ISO-1（0．2ml，20mg／kg）、5％DMSO和无菌生理盐水（NS）。治疗后每周两次观察小鼠盲肠肿瘤大小，第4周时处死小鼠，ELSIA法测定小鼠血清中VEGF浓度；CD31染色标记血管内皮细胞测定肿瘤微血管密度（MVD）。结果在体外，ISO-1明显抑制CT26细胞增殖。在体内，ISO-1明显抑制小鼠肿瘤生长，第4周ISO-1组和DMSO组的抑瘤率分别为25．22％和9．65％，差异有统计学意义（P〈0．01）；并且，ISO-1组移植瘤质量明显小于DMSO组[（1．50±0．14）g比（1．80±0．14）g，P=0．017]；与DMSO组比较，ISO-1降低小鼠血清中VEGF的水平[（14．62±6．49）ng／L比（63．34±10．22）ng／L，P〈0．01]及肿瘤组织MVD[（16．6±3．7）比（35．8±7．3），P=0．002]。结论ISO-1抑制结直肠癌细胞增殖及原位移植瘤生长，其机制可能为ISO-1抑制MIF生物学活性，从而抑制肿瘤细胞增殖、下调VEGF表达与MVD．Objective To investigate the effects of ISO-1, a selective macrophage migration inhibitory factor（MIF） tautomerase activity inhibitor, on the growth and anginogenesis of colorectal cancer in mouse model, and to explore its probable mechanism. Methods CT26 cells were treated with various concentrations of ISO-1 （0.01 - 100 μmol/L） for 24,48 and 72 hours. MTT assay was used for detecting the inhibition effect of ISO-1 on CT26 cell proliferation. The method of orthotopic transplantation ,with fresh tumor masses planted into the hernial sac of cecum by operation, was used to establish mouse model of colorectal cancer. Thirty mice were divided into three groups randomly and treated with ISO-1 （0.2 ml, 20 mg/kg）, 5% DMSO and NS （ normal sodium） twice a week intraperitoneally. Tumor volumes were measured twice a week. After 4 weeks, the mice were sacrificed and serum VEGF concentrations were tested using ELISA. Immunohistochemical staining of CD31 was used for comparing microvessel density （MVD）of tumor tissues. Results In vitro, ISO-1 significantly inhibited CT26 cell proliferation. Also ISO-1 significantly reduced the tumor volumes in vivo. The inhibition ratio of tumorvolume was 25.22% and 9.65% after 4 weeks in ISO-1 and DMSO group, respectively （ P 〈 0.01 ）. Compared with DMSO treatment, ISO-1 reduced the tumor weights [ （ 1.50 ± 0.14） g vs （ 1.80 ± 0. 14） g, P = 0. 017 ] ; and decreased VEGF levels and MVD of tumor tissues significantly [ VEGF ： （ 14. 62 ± 6.49 ） ng/L vs （ 63.34 ± 10.22 ） ng/L, P 〈 0.01 ; MVD ： 16.6 ± 3.7vs 35.8 ± 7.3, P = 0. 002 ]. Conclusions ISO-1 inhibits CT26 cell proliferation and tumor growth. The probable mechanism may be associated with the inhibition of MIF biological activities, down-regulation of the expression of VEGF and reduction of MVD.

关 键 词：结直肠肿瘤 巨噬细胞移动抑制因子 血管生成抑制剂 ISO-1 微血管密度 

分 类 号：R735[医药卫生—肿瘤]