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

Abstract

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