Effect Of Down-regulation Of EEF1A2 On Biological Behavior Of HER2+ Breast Cancer Cells And Inhibitory Activity Of Lapatinib

Breast cancer has been the most frequently diagnosed cancer in females worldwide,while HER2-positive breast cancer accounts for over 20%of the total case number.Lapatinib is a dual EGFR/HER2 inhibitor for HER2+breast cancer therapy,while drug resistance is the main reason for its treatment failure.Researches showed eukaryotic translation elongation factor 1 alpha 2(eEF1 A2)overexpressed in most tumors and promoted the proliferation,metastasis and survival of cancer cells involving many signaling pathways.However,the expression of eEF1A2 in HER2-positive breast cancer and its effects on the HER2 inhibitors are now unclear.This study explored eEF1A2 expressions in breast cancer tissues considering the related clinicopathological characteristics,like HER2 status.It also detected the biological behavior and related proteins expressions of HER2+and HER2-breast cancer cells with the inhibitory effects of lapatinib after the eEF1 A2-knockdown.Results showed eEF1 A2 expression levels in HER2-positive breast cancer tissues were higher than that in HER2-negative ones.The eEF1A2-knockdown enhanced lapatinib’s impacts on proliferation,migration,invasion and apoptosis of HER2+breast cancer cells,SKBR3 and MDA-MB-453.Meanwhile,the inhibitions to HER2/p-AKT and the promotion on p-PKR expressions induced by lapatinib were augmented by eEF1A2-knockdown in HER2+breast cancer cells.At last,with the help of virtual screening techniques and related biological experiments,this study obtained an effective compound NBI-01(C25H21SNO5)that could in vitro suppress proliferation of breast caner cells,bind to eEF1 A2 protein and display synergetic suppressive effects on HER2+breast cancer cells with lapatinib.Overall,this study provided evidences for eEF1A2 being a potential target to improve HER2+breast cancer therapy.