Ionizing Radiation Sensitizes Breast Cancer Cells to Bcl-2 Inhibitor, ABT-737, through Regulating Mcl-1.

Ionizing Radiation Sensitizes Breast Cancer Cells to Bcl-2 Inhibitor, ABT-737, through Regulating Mcl-1. Radiat Res. 2014 Nov 19; Authors: Wu H, Schiff DS, Lin Y, Neboori HJ, Goyal S, Feng Z, Haffty BG Abstract Breast-conserving surgery followed by radiation therapy has become the standard of care for early stage breast cancer. However, there are some patients that develop a local failure. We have previously shown that Bcl-2 overexpression was associated with an increased risk of local recurrence in patients with early stage breast cancer. The purpose of this study was to explore an approach to overcome radiation resistance by targeting pro-survival Bcl-2 family proteins in breast cancer cells. The breast cancer cell lines MCF-7, ZR-75-1 and MDA-MB231 were used in this study. siRNAs were employed to silence myeloid cell leukemia 1 (Mcl-1). A small molecule inhibitor of Bcl-2, ABT-737, was used to target anti-apoptotic Bcl-2 family proteins. Apoptosis was identified by FITC Annexin V, PI staining and Western blot analysis. The sensitivity to ionizing radiation and ABT-737 were measured by clonogenic assays. The effect of radiation and ABT-737 was also tested in a MCF-7 xenograft mouse model. Our data demonstrate that the combination of ABT-737 and radiation-induced apoptosis had an inhibitory effect on breast cancer cell proliferation. However, treatment with ABT-737 resulted in elevated Mcl-1 in breast cancer cell lines. Targeting Mc...
Source: Radiation Research - Category: Physics Authors: Tags: Radiat Res Source Type: research