@Article{Chen2013,
journal="Contemporary Oncology/Współczesna Onkologia",
issn="1428-2526",
volume="17",
number="4",
year="2013",
title="Research on drug resistance mechanism of trastuzumab caused by the activation of PI3K/Akt signaling pathway",
abstract=" Aim of the study:  To discuss the activation of the signal transduction pathway of phosphatidylinositol 3’-kinase/serine-threonine kinase (PI3K/Akt), one of the important targets of drug resistance of trastuzumab, which provides   a theoretical basis for the targeted therapy of drug resistance of trastuzumab in breast cancer.    Material and methods:  Establish the drug-resistance sub-strain BT-HerR of trastuzumab for the continuous treatment of human breast cancer cell strain BT474, conduct Her-2 phenotype analysis on the drug-resistance cell strain BT-HerR with the FISH method, detect the proliferation inhibition   in vitro   of trastuzumab to BT474 and BT-HerR cells with the MTT method, detect the apoptosis variation after interference of trastuzumab with a flow cytometer and detect p-Akt and apoptosis-related protein expression with Western blot after PI3K/Akt inhibitor LY294002 interferes with the cells.    Results : The gene expression of drug-resistance cell strain BT-HerR Her-2 is strongly positive; 72 hours after interference of trastuzumab, the proliferation   in vitro   of the BT474 and BT-HerR cells is inhibited, which is strengthened with the increase of concentration, showing a significant difference (p < 0.01); after treatment of trastuzumab, comparison of the cell apoptosis rate of BT474 and BT-HerR shows a significant difference (p < 0.01); trastuzumab can only inhibit the Akt protein phosphorylation of BT474, while LY294002 can inhibit the BT-HerR and BT474 Akt protein phosphorylation simultaneously.    Conclusions : Akt protein phosphorylation of trastuzumab drug-resistance cells is activated; LY294002, a PI3K/Akt inhibitor, can obviously inhibit Akt protein phosphorylation of trastuzumab drug-resistance cells and there is a clear association between the PI3K/Akt signal transduction pathway and trastuzumab resistance.",
author="Chen, Xi
and Wang, Han
and Ou-yang, Xue-nong
and Xie, Fang-wei
and Wu, Jing-jing",
pages="363--369",
doi="10.5114/wo.2013.35292",
url="http://dx.doi.org/10.5114/wo.2013.35292"
}