Irisin Suppresses The Migration And Invasion Of ER ? Negative Breast Cancer Cells

Background:Breast cancer is a malignant tumor derived from the mammary gland epithelium and is considered as one of the most common malignant tumors in women,it is the second most common cancer in the world.Obesity is an important risk factor for breast cancer.Estrogen-related receptors(ERR?)regulate downstream gene transcription and Wnt signaling by competitively binding to estrogen receptors(ERE)with estrogen receptors(ERa).Irisin,a novel myokine,is closely related to obesity and metabolism,Serum irisin levels are lower in patients with breast cancer.The aim of this study was to investigate the effect of irisin on the biological behavior of ERa negative breast cancer cell and explore the potential mechnism.Methods:BT-20 cells were treated with irisin of different conentrations(0,10 nM,20 nM,50 nM),proliferation and apoptosis was detected by CCK-8 and annexin V/7-AAD staining.Wound healing assay and transwell assay was used to test migration and invasion.Realtime PCR and western blot was performed to examine the transcription and expression level of ERRa,Wntll,epithelial mesenchymal transition(EMT)transcription factors(Snail,Slug,Twist,E-cadherin,Vimentin)and Matrix metalloproteinases(MMP2?MMP9?MMP13)Results:Irisin did not affect cell proliferation and apoptosis,but inhibited migration and invasion(p>0.05).However,irisin significantly inhibited the migration and invasion of BT-20 cells(p<0.05).Irisin significantly reduced the transcription and expression of estrogen-related receptors ERRa and Wntll in BT-20 cells(p<0.05).Irisin significantly downregulated the mRNA levels of Snail,Slug,Twist,E-cadherin,MMP2,MMP9 and MMP13 in BT-20 cells(p<0.01).The protein expression levels of slug,Twist,E-cadherin,MMP2 and MMP9 were significantly decreased after treatment with irisin(p<0.01).Irisin enhanced the inhibition effect of adriamycin on the invasion and metastasis of BT-20 cells(p<0.05),but did not enhance the induction of apoptosis in BT-20 cells(p>0.05).Conclusion:Irisin did not affect the proliferation and apoptosis in ERa negative breast cancer cell BT-20.Irisin inhibited migration and invasion of BT-20 cells and enhanced the inhibition efftet of doxorubicin on tumor migration and invasion.This effect was potentially achieved through the ERRa-Wnt11 and EMT signaling pathway.