The Influence And Mechanisms Of Moxifloxacin Combined With Epirubicin In Human Triple-negative Breast Cancer Cell Line MDA-MB-231

Objective: This study intends to investigate the effect of moxifloxacin alone or combine with epirubicin on human breast cancer line MDA-MB-231 cells' growth and invasion ability,and to explore the possible mechanism for reducing the side effects of chemotherapy and provide theoretical basis for improving the prognosis of patients with triple negative breast cancer.Methods:1?Using SRB method to compare the inhibition ability of moxifloxacin and epirubicin alone or combined on the cell proliferation.2?Detecting the influence of moxifloxacin and epirubicin alone or combination on the cell's expression of Ki67 protein by using immunocytochemistry method.3?Using Transwell invasion experiment to compare the influence of moxifloxacin and epirubicin alone or combined on cell's invasion ability.4?Using immunocytochemistry and Western Blot method to investigate the influence of moxifloxacin on MMP2 protein's expression.4?Using Western Blot method to detect the expression of Jak2,P-stat3,Bcl-2 and Bcl-xl proteins which were JAK–STAT3 signal transduction pathways related proteins for investigating the effect of moxifloxacin on the signal transduction pathways.Results:1?According to the results of SRB detection,both moxifloxacin and epirubicin showed significant time/dose-dependent proliferation inhibition against MDA-MB-231 cells in vitro(P < 0.01).The IC50 of each agent at 24 h,48h,72 h were Moxifloxacin: 156.843,65.055,55.572?mol/L;Epirubicin : 2.832,1.091,0.738?mol/L,respectively.Epirubicin(2.5 mol/L)combine with moxifloxacin(12.5 mol/L)in 24 h showed synergy effect(q value>1.15).2?As the immunocytochemistry assay showed,the Ki67 protein's Optical Density(OD)value of each groups were Control group: 0.296±0.011;Moxifloxacin group:0.282±0.001;Epirubicin group: 0.256±0.004;Combination group: 0.238±0.010,which showed significant difference(P<0.05).3?Transwell invasion experiment showed the number of cells through the membrane were Control group: 156.5±12.625;Moxifloxacin group:131.5±22.555;Epirubicin group: 39.3±15.910;Combination group: 16.6±7.545.The cell numbers between each groups showed significant difference(P<0.05).4?Moxifloxacin decreased MDA-MB-231 cells' expression of MMP-2 protein,which had negative correlatation with the concentration(P<0.05).5?Moxifloxacin decreased the expression of Jak2,P-stat3,Bcl-2 and Bcl-xl proteins,which had negative correlatation with the concentration(P<0.05).Conclusion:1?Both moxifloxacin and epirubicin showed significant time/dose-dependent inhibition in MDA-MB-231 cells' proliferation in vitro.Coadministration moxifloxacin with epirubicin showed additive or synergy inhibitory effect.2? Moxifloxacin could decrease MDA-MB-231 cells' invasion ability by reduce the expression of MMP2 protein,which had positive correlation with the concentration.This efficacy could be enhanced when combined with epirubicin.3?Moxifloxacin could down-regulated the expression of JAK-STAT3 pathway related protein,which inhibited MDA-MB-231 cells' proliferation.