低氧微环境促进人乳腺癌细胞系MCF-7的侵袭和增殖

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (4): 539-544.

低氧微环境促进人乳腺癌细胞系MCF-7的侵袭和增殖

王海燕, 黄明全, 潘广锐, 汪贵林, 梁斌, 权毅^*

西南医科大学附属医院乳腺外科, 四川泸州 646000

收稿日期:2020-04-24 修回日期:2020-07-31 出版日期:2021-04-05 发布日期:2021-04-05
通讯作者: ^*yancheng1118@163.com
基金资助:
西南医科大学应用基础研究计划项目(2017-ZRQN-114)

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

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

Received:2020-04-24 Revised:2020-07-31 Online:2021-04-05 Published:2021-04-05
Contact: ^*yancheng1118@163.com

摘要/Abstract

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% CO₂,94% N₂)、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。

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

Abstract: Objective To investigate the expression of HIF-1 α, 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% O₂ 5% CO₂ 94% N₂) 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 the basement 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.

Key words: breast cancer, hypoxia inducible factor 1α, vascular endothelial growth factor, tumor microenvironment

中图分类号:

R737.9

王海燕, 黄明全, 潘广锐, 汪贵林, 梁斌, 权毅. 低氧微环境促进人乳腺癌细胞系MCF-7的侵袭和增殖[J]. 基础医学与临床, 2021, 41(4): 539-544.

WANG Hai-yan, HUANG Ming-quan, PAN Guang-rui, WANG Gui-lin, LIANG Bin, QUAN Yi. Hypoxia microenvironment promotes invasion and proliferation of human breast cancer cell line MCF-7[J]. Basic & Clinical Medicine, 2021, 41(4): 539-544.

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