低氧微环境促进人乳腺癌细胞系MCF-7的侵袭和增殖  

Hypoxia microenvironment promotes invasion and proliferation of human breast cancer cell line MCF-7

作　　者：王海燕 黄明全 潘广锐 汪贵林 梁斌 权毅 WANG Hai-yan;HUANG Ming-quan;PAN Guang-rui;WANG Gui-lin;LIANG Bin;QUAN Yi(Department of Breast Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China)

机构地区：[1]西南医科大学附属医院乳腺外科,四川泸州646000

出　　处：《基础医学与临床》2021年第4期539-544,共6页Basic and Clinical Medicine

基　　金：西南医科大学应用基础研究计划项目(2017-ZRQN-114)。

摘　　要：目的探讨合并2型糖尿病乳腺癌组织中HIF-1α、PAR-1、VEGF的表达及低氧微环境对人乳腺癌细胞系(MCF-7)侵袭和增殖的影响。方法乳腺癌合并2型糖尿病手术切除送检的标本37份,免疫组化检测乳腺癌和癌旁组织中HIF-1α、PAR-1、VEGF表达,测定微血管密度(MVD);将MCF-7细胞分为对照组(5.6 mmol/L葡萄糖)、高糖组(30 mmol/L葡萄糖)、低氧组(1%O2,5%CO_(2),94%N_(2))、高糖低氧组。采用显微镜观察各组细胞形态;CCK-8法检测细胞增殖;Transwell小室法检测细胞侵袭能力;RT-qPCR和Western blot检测HIF-1α、PAR-1、VEGF mRNA和蛋白表达。结果乳腺癌组织中HIF-1α、PAR-1、VEGF表达及MVD计数高于癌旁组织(P<0.05);高糖低氧组MCF-7穿过基膜的细胞数及细胞存活率明显升高(P<0.01);低氧组、高糖低氧组HIF-1α、PAR-1、VEGF mRNA及蛋白表达较空白组明显升高(P<0.05)。结论低氧高糖促进MCF-7细胞增殖和侵袭及HIF-1α、PAR-1、VEGF表达,可为临床2型糖尿病乳腺癌检测及治疗提供靶点。Objective To investigate the expression of HIF-1α,PAR-1 and VEGF in breast cancer tissues from patients with type 2 diabetes and the effect of hypoxia microenvironment on the invasion and proliferation of human breast cancer cell line(MCF-7).Methods Thirty-seven specimens of breast cancer from patients with complicated with type 2 diabetes mellitus were examined by surgical resection.The expression of HIF-1α,PAR-1,VEGF and microvessel density(MVD)in breast cancer and paracancerous tissues were examined by immunohistochemistry.MCF-7 cells were divided into control group(5.6 mmol/L glucose),high glucose group(30 mmol/L glucose),hypoxia group(1%O25%CO_(2)94%N_(2))and high glucose plus hypoxia group.The cell morphology was observed by microscoped,the cell proliferation was detected by CCK-8 method,the invasive ability of cells was detected by Transwell chamber test,and the expression of HIF-1α,PAR-1,VEGF mRNA and protein were detected by RT-qPCR and Western blot.Results The expression of HIF-1α,PAR-1,VEGF and MVD count in breast cancer tissues were higher than those in periaracancerous tissues(P<0.05);the number of cells passing through thebasement membrane and the cell survival rate of MCF-7 in the high glucose hypoxia group were significantly higher than those in the control group(P<0.01);and the expressions of HIF-1α,PAR-1,VEGF mRNA and protein in the hypoxia group and hypoxia high glucose group were significantly higher than those in the control group(P<0.05).Conclusions Hypoxia and high glucose can promote the proliferation and invasion and the expression of HIF-1α,PAR-1,VEGF of MCF-7 cells,which is a potential target for clinical detection and treatment of breast cancer of patients with type 2 diabetes.

关 键 词：乳腺癌 低氧诱导因子1Α 血管内皮生长因子 肿瘤微环境 

分 类 号：R737.9[医药卫生—肿瘤]