多不饱和脂肪酸n-6／n-3对子宫内膜癌小鼠皮下种植瘤中AKT、mTOR表达的影响

摘要

目的：研究不同比例n-6-3多不饱和脂肪酸（ PUFAs）对人子宫内膜癌瘤组织中AKT、mTOR表达的影响。方法建立人子宫内膜癌小鼠皮下种植瘤模型，40只实验BALB/C模型小鼠随机分为A组（ n-6 PU-FAs）、B组（10∶1 n-6-3 PUFAs）、C组（对照）、D组（1∶1 n-6-3 PUFAs）、E组（n-3 PUFAs），每组8只。A、B、D、E组分别灌胃给予不同比例 PUFAs，C组给予等量生理盐水。6周后处死小鼠，切取皮下种植瘤组织，苏木精-伊红染色镜下定位观察肿瘤组织形态，免疫组化SP法检测种植瘤组织中AKT、mTOR蛋白表达， RT-PCR法检测各组种植瘤组织中AKT、mTOR的mRNA表达。结果苏木精-伊红染色结果确认皮下种植瘤模型建立成功；免疫组化SP法和RT-PCR结果显示n-6 PUFAs和10∶1 n-6-3 PuFAs 组中AKT、mTOR的蛋白和mRNA的表达增加，与对照组相比差异有统计学意义（ P＜0．05）；n-3 PUFAs和1∶1 n-6-3 PUFAs 组中的中AKT、mTOR的蛋白和mRNA表达下降，与对照组相比差异有统计学意义（ P＜0．05）。结论不同比例的 n-6-3 PUFAs对人子宫内膜癌的作用机制可能是通过PI3k/AKT/mTOR信号通路调节 AKT、mTOR的表达而起作用的。%Objective To investigate the effects of different ratios of n -6-3 polyunsaturated fatty acids on the expressions of AKT and mTOR in mice with endometrial carcinoma .Methods A tumor model of mice was established where the mice were subcutaneously injected with human endometrial carcinoma .The mice ( n=40 ) were randomly di-vided into five groups according to their different treatments:group A (n-6 PUFAs), group B( 10∶1 n-6-3 PU-FAs), group C (control group), group D (1∶1 n-6-3 PUFAs) and group E (n-3 PUFAs), eight mice in each group.The mice in experimental groups were intragastrically administrated with different proportional PUFAs ,while the mice in control group were fed with an equal amount of normal saline .Six weeks later , these mice were sacrificed and the subcutaneous tumor tissues were excised .The histomorphological changes of the tissues were detected by hematoxylin -e-osin staining .The expressions of AKT and mTOR were examined by SP -IHC method , while the amounts of AKT and mTOR mRNA were accessed by RT -PCR.Results The establishment of the model of mice with human endometrial carcinoma was confirmed by HE staining .Then enhanced expressions of AKT and mTOR at protein and mRNA levels were found in the n-6 PUFAs group and the 10∶1 n-6-3 PUFAs group, when compared with the control group (P<0.05).However, the n-3 PUFAs group and the 1∶1 n-6-3 PUFAs group presented reduced protein and mRNA expressions of AKT and mTOR than the control group (P<0.05).C onclusion The effects of different ratios of n -6-3 PUFAs on endometrial carcinoma may be attributed to various abilities of the PUFAs to regulate the expressions of AKT and mTOR through the PI3k/AKT/mTOR signal pathway.