Inhibition of doxorubicin-induced HER3-PI3K-AKT signalling enhances apoptosis of ovarian cancer cells.

ABSTRACT: Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian cancer cells. We further show that the induction of this anti-apoptotic signalling pathway is based on upregulated expression of HER3 ligands, their shedding by the metalloprotease ADAM17, and is dependent on the HER2 receptor. The doxorubicin-mediated activation of this important survival cascade can be blocked by the kinase inhibitors lapatinib or erlotinib as well as by the therapeutic monoclonal antibody trastuzumab. Inhibition of the doxorubicin-induced activation of HER

SUBMITTER: Bezler M 

PROVIDER: S-EPMC5528396 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature