摘要目的 观察裸鼠的人胰腺癌细胞SW1990移植瘤内注射靶向5-脂氧合酶(5-LOX)的短发夹RNA(shRNA)对移植瘤以及瘤组织5-LOX和血管内皮生长因子(VEGF)表达的影响,探讨其临床应用价值.方法 将胰腺癌细胞SW1990接种至裸鼠背部皮下,待移植瘤生长至100 mm3左右后随机分为shRNA1组、shRNA2组、阴性对照shNC组和脂质体组.每组6只,雌雄各半.实验组瘤内注射相应shRNA 50μg/次,1次/3 d,共7次.对照组瘤内注射脂质体液100 μl/只.每3 d测体重及移植瘤长、短径一次.第29天处死动物,取肿瘤组织,称瘤重.应用免疫组化和RT-PCR法检测移植瘤组织5-LOX、VEGF的mRNA和蛋白的表达.结果 shRNA1组、shRNA2组、shNC组和脂质体组的瘤重分别为(32.5±19.0)mg、(30.1±14.1)mg、(50.5±15.6)mg和(71.7±25.4)mg,shRNA1组、shRNA2组、shNC组抑瘤率分别为54.7%、58.0%和29.5%,shRNA1组、shRNA2组较shNC组和脂质体组相差显著(P值均＜0.05).shRNA1组和shRNA2组移植瘤的5-LOX、VEGF mRNA和蛋白的表达较shNC组和脂质体组均显著减少,但两治疗组之间未见明显差异,shNC组和脂质体组之间也无明显差异.结论 靶向5-LOX的RNA干扰治疗通过直接抑制5-LOX的表达、间接抑制VEGF的表达而抑制SW1990裸鼠移植瘤的生长.

abstractsObjective To study the efficacy of RNA interference targeting 5-LOX on 5-LOX and VEGF expression as well as the growth of tumor xenografts in the nude mice,in order to evaluate the value of the clinical application.Methods SW1990 cells were injected into the back of BALB/c nude mice.Once the visible tumors were evidenced about 100mm3,the animals were divided randomly into 4 groups (6 animals/group) and treated with shRNA1 and shRNA2 targeting 5-LOX,negatrve control shRNA (shNC) or control LipofectamineTM 2000 (Lipo) by intratumoral injection.Observing the effect of the shRNA on the growth of tumor xenografts,investigating the expression of 5-LOX and VEGF by immunohistochemistry and RT-PCR.Results Two nude mice were dead in shNC group and Lipo group because of the wasting disease.Other nude mice had no changes in body weight,spirit,appetite,and activity.The growth of tumor xenografts was suppressed potently when administered with shRNA.Compared with shNC and Lipo group,the mean tumor size in groups treated with shRNA was reduced markedly at every point of test time.Between two treat groups,they did not have significant difference.5-LOX and VEGF were both expressed in the pancreatic cancer tissue.The level of the 5-LOX expression in shRNA groups was stronger than that in shNC or Lipo group.The VEGF had the game situation.Between the two treat groups,the difference was not significant.Conclusions RNA interference targeting 5-LOX can inhibit the growth of tumor tumor xenografts in the nude mice by depressing the expression of 5-LOX directly and depressing the expression of VEGF indirectly.