The Study On Predictive Value And Mechanism Of The Plasma CCL5 In Neoadjuvant Chemotherapy Of Breast Cancer

Chemotherapy is a key part of comprehensive treatment in breast cancer.Neoadjuvant chemotherapy is the preoperative chemotherapy for patients with locally advanced breast cancer.there is no appropriate predictive markers of NCT.In order to investigate effective indicators to predict the response of NCT,we used the RayBiotech Human Cytokine Antibody Array to screen the different concentrations of cytokine in plasma between patients with or without CTCs before NCT.The concentration of plasma CCL5 was increased in patients with CTC-positive patients.Further the CCL5 level of patients with different pathological response to NCT was determined.The plasma levels of CCL5 were significantly reduced following NCT in the High-R(pre-NCT 6.33±3.96ng/ml,post-NCT 2.66±2.87ng/ml,t=2.626,p=0.030),but not in the Low-R(pre-NCT 3.85±2.43ng/ml,post-NCT 4.82±4.57ng/ml,t=-0.564,p=0.591).In vitro experiment,A CCK-8 assay was used to examine the effects of epirubicin at different concentrations(0.1-1.6 ?g/ml)on cell proliferation of MCF-7 and ZR-75-1.The results suggested the concentration of 50 ng/mL CCL5 significantly reduced the cytotoxicity effect of epirubicin.The transwell assay verified CCL5 treatment could promote the migration and invasion of breast cancer cells.The mRNA levels of CDH1,Vimentin were verified in MCF-7 and ZR-75-1.The mRNA of CDH1 was decreased in ZR-75-1CCL5,and the mRNA of Vimentin was increased in MCF-7CCL5 and ZR-75-1CCL5 The intervention of epirubicin could downregulate the mRNA of CDH1 in both MCF-7 and ZR-75-1,upregulate the mRNA of Vimentin in ZR-75-1.The intervention of epirubicin in MCF-7 cells treated by CCL5 could make this EMT change in a deep degree.In protein level,comparing with negative control group,the expression level of vimentin was increased in the cells treated by CCL5 in MCF-7 and ZR-75-1,the expression level of E-cadherin was decreased in in the cells treated by CCL5 in ZR-75-1.After the intervention of epirubicin,the expression of vimentin was increased and the expression of E-cadherin was decreased in both MCF-7 and ZR-75-1.On this basis,more drastic changes in E-cadherin and Vimentin could be detected in MCF-7 treated by CCL5.The phpsphorylation of ezrin(Y567)increased significantly in MCF-7 and ZR-75-1 cells treated by CCL5.The mesenchymal marker cortactin was increased in MCF-7 and ZR-75-1 cells treated by CCL5.After the chemotherapy of epirubicin,there is still an up-regulatory mechanism of CCL5 in both MCF-7 and ZR-75-1.