Chemosensitization of T-47D breast carcinoma cells to TRAIL and fas receptor-induced killing

Background: Although chemotherapeutic agents are known to sensitize some tumour types to killing through cell surface death receptors for Fas ligand and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chemosensitization of breast carcinoma cells has not yet been explored. Materials and Methods: Mitochondrial thiazole tetrazolium assays were used to measure changes in MCF-7 and T-47D breast carcinoma cell viability. Semiquantitative RT-PCR was used to determine Fas and TRAIL receptor mRNA expression. Results: Treatment with suboptimal concentrations of etoposide or doxorubicin rendered T-47D cells sensitive to anti-Fas antibody or TRAIL, consistent with Fas and TRAIL-R1 mRNA expression by T-47D cells following drug treatment. In contrast, neither drug sensitized MCF-7 cells to TRAIL- or anti-Fas antibody, most likely due to diminished Fas and TRAIL-R1 expression following drug treatment. Conclusion: These findings suggest that some breast carcinomas may respond favorably to a combination of chemotherapy and immunotherapy.