Apoptotic Resistance of Metastatic Tumor Cells in Triple Negative Breast Cancer: Roles of Death Receptor-5

BACKGROUND: Metastasis is a major cause of death from cancer in triple-negative breast cancer (TNBC). Apoptosis evasion is a critical feature of metastatic tumor cells. Chemopreventive and apoptotic potential of curcumin has been shown in breast cancer. However, the precise mechanism of these effects against metastatic tumor cells has not been clearly addressed yet. METHODS: 4T1 cell line was used for induction of metastatic animal model of breast cancer. Primary and metastatic tumor cells were extracted from subcutaneous tumor and lung of cancerous mice, respectively. MTT assay was used to determine the effect of curcumin on viability of tumor cells. Quantitative real-time polymerase chain reaction was performed to analyze the effect of curcumin on death receptor-5 (DR-5) gene expression. RESULTS: Our data revealed that, compared with primary tumor cells, metastatic tumor cells were more resistance to apoptosis effects of curcumin. The DR-5 gene expression was up-regulated in both primary and metastatic tumor cells after curcumin treatment, but this up-regulation was significantly higher in primary tumor cells compared with metastatic cells. CONCLUSION: These findings provided important insights regarding the molecular mechanism of apoptosis resistance of metastatic tumor cells and can be used for designing a targeted therapeutic strategies in combat with metastatic TNBC.