TNFSF15表达下调或缺失对卵巢癌组织中肿瘤新血管形成的影响  

The Effect of Down Regulation of TNFSF15 on Tumor Neovascularization of Ovarian Cancer

作　　者：宋娟[1] 张秋月[1] 顾欣[1] 许静静[1] 李凤舞[1] 谷超[1] 邓为民[1] 

机构地区：[1]天津医科大学基础医学院免疫学教研室,300070

出　　处：《天津医药》2012年第9期908-911,共4页Tianjin Medical Journal

基　　金：国家自然科学基金资助项目(项目编号:30670801);天津市科学技术委员会基金资助项目(项目编号:06YFJMJC08300)

摘　　要：目的:探讨肿瘤坏死因子超家族-15(TNFSF15)在人卵巢癌标本中的表达及在小鼠体内TNFSF15对卵巢癌血管生成及卵巢癌生长的影响。方法:应用免疫组化法检测正常组(12例)、卵巢癌组(94例)中TNFSF15的表达情况及微血管密度(MVD);雌性C57BL/6小鼠24只随机分为对照组、重组TNFSF15注射组(实验组)、TNFSF15-shRNA处理组(A组)、shRNA-对照组(B组),每组6只,各组均采用皮下注射ID8细胞制备小鼠荷瘤模型,实验组采用腹腔注射重组TNFSF15蛋白,A、B组采用TNFSF15-shRNA干扰其内源性表达的方法,通过检测小鼠肿瘤组织MVD值并测量肿瘤体积大小,观察其对小鼠卵巢癌细胞系ID8在小鼠C57BL/6体内血管生成及肿瘤生长的影响。结果:与正常卵巢组织相比,卵巢癌组织标本中TNFSF15表达显著降低(P<0.01),且Ⅲ/Ⅳ期TNFSF15阳性表达率较Ⅰ/Ⅱ期降低(P<0.05);实验组较对照组小鼠肿瘤组织中MVD值降低且肿瘤体积减小(P<0.05),而A组较B组MVD值升高且肿瘤体积增大(P<0.05)。结论:卵巢癌微环境中TNFSF15表达下调或缺失是肿瘤新血管形成的前提条件。Objective： To study the expression of tumor necrosis factor superfamily-15 （TNFSF15） in human ovarian cancer specimens and the effects of TNFSF15 on tumor angiogenesis and growth in mice. Methods： The expression of TNFSFI5 and the value of microvesse] density （MVD） were detected by the method of immunohistochemistry in normal ovary group （n=12） and ovarian cancer group （n=94）. Twenty-four female C57BId6 mice were randomly divided into 4 groups： control group, recombinant TNFSFI＇5-treated group （experimental group）, TNFSF15 shRNA-treated group （group A） and control-shRNA （group B）. There were 6 mice for each group. The tumor-bearing mouse model was made by injecting subcutaneously ID8 cells into the flank of mia. The recombinant TNFSF15 was used to treat IDS-beafing C57BId6 mice via intraperitoneal injection. TNFSFI5-shRNA was used in group A and group B. The influences of TNFSF15 on tumor angiogenesis and growth were assessed by measuring MVD values and tumor volumes in mice. Results： Compared to the normal ovary tissues, the expression level of TNFSF15 decreased significantly in cancer specimens （P 〈 0.01）, and the positive expression of TNFSF15 protein was lower in stage III/IV than that of stage I/II （P 〈 0.05）. The values of MVD and the tumor volumes were decreased in experimental group than those of control group（P 〈 0.05）. On the other hand, the MVD values and tumor volumes were higher in group A than those of group B（P 〈 0.05）. Conclusion： The down regulation or absent of TNFSFI5 in ovarian cancer microenvironment is a pre-requisite for tumor neovaseularization.

关 键 词：卵巢肿瘤 癌 免疫组织化学 疾病模型 动物 新血管形成 肿瘤坏死因子超家族-15 

分 类 号：R593.2[医药卫生—内科学]