c-FLIP gene silencing eliminates tumor cells in breast cancer xenografts without affecting stromal cells.

Cellular FLICE-like inhibitory protein (c-FLIP) is an inhibitor of death receptor-mediated apoptosis and exerts its anti-apoptotic function by blocking the activation of caspase-8. We recently showed that the siRNA-mediated knockdown of c-FLIP in MCF-7 breast cancer cells growing in vitro triggered apoptosis. The aim of this study was to determine if the in vivo knockdown of c-FLIP in MCF-7 breast cancer xenografts affected tumor viability. Immunohistochemical detection of c-FLIP in the tumor sections revealed that the knockdown of c-FLIP eliminated the neoplastic cells within the breast cancer xenografts without affecting the normal stromal and fibroblastic cells. These results indicate that c-FLIP is required for breast cancer growth and is a relevant therapeutic target for the treatment of breast cancer.