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

Document Type: Research Articles

Authors

1 Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

2 Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

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.

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