Synthetic triterpenoid CDDO as effective therapy for HER2 expressing resistant breast cancer.

3799Overexpression of the HER2 proto-oncogene confers resistance of breast cancer cells to antiestrogens and chemotherapy and translates into aggressive disease with short survival. Despite clinical benefit of the HER2 inhibitor Trastuzumab in metastatic breast cancer with overexpressed HER2, most patients are developing resistance. We have reported that the novel synthetic triterpenoid CDDO (2-cyano-3,12- dioxooleana-1,9-dien-28-oic acid) induces growth arrest and apoptosis in breast cancer cells. We studied the effects of CDDO on proliferation and differentiation of breast cancer cell lines with different HER2 expression levels including stably transfected MCF7/HER2 and MDA-MB-435/HER2 cells, vector controls and SKBR3 cells with constitutive HER2 overexpression. Results demonstrate dose-dependent inhibition of colony formation by CDDO at submicromolar concentrations, with HER2 …