Effect of basic fibroblast growth factor on hypoxia-inducible factor (HIF)-1α expression (Exp) and HIF-1 transcription in breast Cancer cell through PI-3 K Akt signaling

Abstract

Objective

To investigate the effect of basic fibroblast growth factor (bFGF) on hypoxia-inducible factor (HIF)-1α expression (Exp) and HIF-1 transcription in breast cancer (BC) cells.

Methods

Human BC cell line T47D was utilized as the research object. Western blot and dual-luciferase system were utilized to detect HIF-1α Exp induced by bFGF in BC cells under hypoxia and normal oxygen conditions, as well as the Exp of phosphorylated ERK1/2, Akt, and p38 proteins, HIF-1α Exp induced by bFGF under kinase inhibitors' action, and HIF-1 transcription, thereby summarizing the impact of bFGF on BC cells and its association with PI-3 K Akt signaling pathway (SPW).

Results

The maximum Exp fold was 4.9 when the induced dose of bFGF was 10 ng/mL under hypoxia, and the maximum Exp fold of HIF-1α was 7 at 3 h (180 min). Under normal oxygen condition, cycloheximide inhibited HIF-1α protein Exp, and the reduction was up to 50 % within 30 min. Various doses of kinase inhibitor SU5402 inhibited HIF-1α protein Exp, and the inhibition rate was 100 %. The kinase inhibitors SU5402, PD98059, and LY294002 all had marked effects on bFGF-induced HIF-1 transcription.

Conclusion

Both MEK1/ERK and PI-3 K/Akt SPW play crucial roles in bFGF-mediated HIF-1 activation. BFGF had a notable activation of HIF-1. PI-3 K/Akt and MEK1/ERK SPW worked together to regulate this process by various mechanisms.