纳米金结合恩度抑制小鼠黑色素瘤肺转移  

Inhibitory effect of Au NPs-Endostar on melanoma lung metastasis in mice

作　　者：李鑫[1] 潘运龙[1] 覃莉[1] 李伟[1] 吴秀[1] 杨文德[1] 潘璠 LI Xin;PAN Yun-long;QIN Li;LI Wei;WU Xiu;YANG Wen-de;PAN Fan(Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China)

机构地区：[1]暨南大学附属第一医院胃肠外科,广东广州510630

出　　处：《中国病理生理杂志》2017年第8期1393-1398,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81472849);广东省自然科学基金资助项目(No.2014A030313383;No.2014A030313382)

摘　　要：目的:观察纳米金结合恩度对小鼠黑色素瘤肺转移的影响并探讨其机制。方法:C57BL/6小鼠24只,构建小鼠黑色素瘤B16-F10细胞自发性肺转移模型,随机分为恩度组、纳米金组、纳米金结合恩度组和模型组。成瘤后各组小鼠均经尾静脉注射相应药物0.1 mL(每天1次)。9 d后麻醉小鼠并切取原位肿瘤,继续饲养2周后处死小鼠取肺组织观察转移情况。HE染色观察原位肿瘤坏死情况,免疫染色检测肿瘤CD31、碳酸酐酶IX(CA-IX)、vimentin和闭锁小带蛋白1(ZO-1)的表达。结果:与模型组相比,药物处理组小鼠的肺转移灶均明显减少,其中纳米金结合恩度组的肺转移抑制率最高,肿瘤坏死明显减少,肿瘤中CD31、CA-IX和vimentin的表达量显著降低,ZO-1的表达量显著升高。结论:与单用恩度或纳米金相比,纳米金结合恩度可明显抑制小鼠黑色素瘤肺转移,其机制可能为使肿瘤新生血管减少及血管正常化,改善肿瘤缺氧,从而抑制肿瘤上皮-间充质转化,使肿瘤细胞间紧密连接增加而侵袭性减低。AIM:To observe the influence of gold nanoparticles combined with Endostar(A uN Ps-E ndostar)on the melanoma lung m etastasis of mice and the underlying mechanism.METHODS:C57BL/6mice(n=24)were selectedfor constructing the model of spontaneous lung metastasis of melanoma B16-F10cells.Subsequently,the mice wererandomly divided into Endostar group,AuNPs group,AuNPs-Endostar group and model group.After the formation of m elanoma,the mice in each group were injected with different drugs through tail vein for0.1mL daily.After9d,the micewere narcotized for cutting the tumors in situ.After the operation,they were raised for2weeks before killed for obtainingthe lung tissues to observe the situation of the metastasis.HE staining was utilized for observing the necrosis status of thetumors in situ,while immunostaining was applied for testing the expression of C D31,carbonic anhydrase-IX(CA-IX),vimentin and zonula occludens-1(ZO-1)in the tumors.RESULTS:Compared with model group,the pulmonary metastasisin the groups with medical treatm ent was obviously reduced.In AuNPs-Endostar group,the m etastasis inhibition rate wasthe highest,and the tumor necrosis was also decreased obviously,with the significant reduction of C D31,CA-IX and vimentinexpression in the tumors and significant increase in ZO-1expression.CONCLUSION:Compared with using E ndostaror AuNPs alone,the combination of AuNPs with Endostar significantly improves the curative effect of inhibiting thepulmonary metastasis of melanoma in the mice.The m echanism may be related to reducing the tumor angiogenesis,normalizingthe blood vessels and improving tumor hypoxia,thus inhibiting the tumor epithelial-m esenchym al transition,increasingthe tight junctions between tumor cells and decreasing the invasiveness.

关 键 词：纳米金 恩度 黑色素瘤 肿瘤转移 上皮-间充质转化 

分 类 号：R730.23[医药卫生—肿瘤]