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

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.

Keywords

• breast cancer|hypoxia inducible factor 1α|vascular endothelial growth factor|tumor microenvironment