丙酮酸乙酯对严重联合免疫缺陷小鼠原位移植胃癌转移的抑制作用  

Inhibitory effects of ethyl pyruvate on gastric cancer metastasis in a severe combined immunodeficiency mice orthotopic implantation model

作　　者：杨宇宸[1] 张靖[1] 朱金水[1] 周洲[1] 陈维雄[1] 

机构地区：[1]上海交通大学附属第六人民医院消化内科,200233

出　　处：《中华临床医师杂志（电子版）》2012年第15期84-87,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：上海交通大学医学院博士创新基金项目(BXJ201234);上海市科委基金资助项目(10140902500)

摘　　要：目的探讨丙酮酸乙酯(EP)对严重联合免疫缺陷(SCID)小鼠原位移植胃癌生长及其肝转移的抑制作用及分子机制。方法用SGC-7901人胃癌组织原位移植SCID小鼠建立胃癌肝转移模型。术后1周,动物分别腹腔注射不同浓度的EP,3周后取出胃癌和转移肝组织,检测胃癌组织体积、重量及其转移肝结节数量;实时定量PCR和免疫组化法检测不同组中高迁移率族蛋白B-1(HMGB1)、受体糖基化终产物受体(RAGE)、NF-κB、血管内皮生长因子(VEGF)及膜1型基质金属蛋白酶(MT1-MMP)的表达水平。结果与对照组比较,EP治疗组的胃癌组织重量、大小及其转移肝结节数量明显减少(P均<0.01)。并且EP抑制胃癌及转移肝组织中HMGB1、RAGE、VEGF及MT1-MMP的表达,但对NF-κB表达无明显影响。结论 EP可能通过下调HMGB1-RAGE通路抑制SCID小鼠原位移植胃癌生长及其肝转移,对癌症可能具有治疗作用。Objective To explore the effects and molecular mechanisms of ethyl pyruvate （EP）on gastric cancer growth and liver metastasis in a severe combined immunedeficiency （SCID）mice orthotopic implantation model. Methods SGC-7901 human gastric cancer tissues were orthotopically implanted into SCID mice to establish gastric cancer and metastatic liver tumor model. At first week after implantation, mice were randomly separated into three groups with six mice per group and they were injected i. p. with 40-80 mg/kg EP once a day. Control mice were injected with the same amount of PBS. After three weeks, mice were sacrificed by cervical dislocation, and gastric cancer tumor volume, weight and metastatic liver tumor nodules were respectively measured. The expression levels of high mobility group box-B1 （HMGB1） ,receptor for advanced glycation endproducts（RAGE） , nuclear factor-kappa B （NF-KB） ,vascular endothelial growth factor（ VEGF） and membrane type-1 matrix metalloprotease （MT1-MMP）were detected by real-time PCR and immunohistochemistry assays. Results The volume and weight of gastric cancer and metastatic liver tumor nodules were significantly reduced in EP treatment groups compared with the control group （each P 〈 0. 01 ）. EP also inhibited the expression of HMGB1, RAGE, VEGF and MT1-MMP, but exerted no effect on expression of NF-KB in gastric cancer and metastatic liver tumor tissues. Conclusions EP may inhibit SCID mice gastric cancer growth and liver metastasis via down-regulation of the HMGB1-RAGE pathway, and play a crucial role in the treatment of cancer.

关 键 词：重症联合免疫缺陷 胃肿瘤 丙酮酸乙酯 肿瘤转移 

分 类 号：R735.2[医药卫生—肿瘤]