Effect and significance of ErbB2 kinase inhibitor AG825 on proliferation of non-overexpression ErbB2 breast cancer cell

Objective:To explore whether there was activation of NRGs/ErbB2 ligand signal transduction pathway on non-overexpression ErbB2 breast cancer cell in order to investigate the effect of activation and proliferation of NRGs on ErbB2 receptor signal transduction pathway.Methods:Non-overexpression ErbB2 breast cancer cell MDA-MB-231 and MCF-7 were studied in the study.Growth curves of the two cell lines were obtained by the trypan blue exclusion method.The expressions of neuregulin were detected by immunocytochemistry and Western blot.MDA-MB-231 cells and MCF-7 cells were treated with ErbB2 kinase inhibitor AG825,The effect of AG825 on the proliferation was investigated by MTT assay to compare the different effects between the two kinds of cells.The intermediate concentration IC50 in 48 hours in MDA-MB-231 cells was determined.MDA-MB-231 cells were treated with 40μmol/L AG825 for 48 hours,and the cell cycle and apoptosis were detected by flow cytometry.Results:Compared with MCF-7 cells,MDA-MB-231 cells presented strong growth ability.MDA-MB-231 cells expressed a relatively higher level of neuregulin,and MCF-7 cells did not express neuregulin.In the Western blot,the positive reaction band was found in 44 kD which coincided with the molecular weight of NRG in MDA-MB-231 cells.When MDA-MB-231 cells and MCF-7 cells were treated with AG825,MDA-MB-231 cells were inhibited more obviously.The intermediate concentration IC50 of AG825 in MDA-MB-231 cells was 56.59 μmol/L.After MDA-MB-231 cells were treated with 40μmol/L AG825 for 48 hours,the cell cycle was arrested in G0/G1 phase(P0.05),and the apoptosis rate was increased(P0.01).Conclusion:Our study indicated in MDA-MB-231 cells neuregulins could activate ErbB2 receptor signal transduction pathway by autocrine or paracrine action,which has relation to malignancy behavior of the cells with higher proliferation and lower apoptosis.