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Resveratrol enhances the sensitivity of doxorubicin‐mediated cell proliferation, invasion, and migration in human breast cancer cell lines
Author(s) -
KIM Hyung Sik,
Kim Tae Hyung
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.964.10
Subject(s) - doxorubicin , resveratrol , viability assay , apoptosis , chemistry , cell migration , cancer research , cell culture , mcf 7 , cytotoxicity , cell growth , cell , pharmacology , cancer cell , mtt assay , cell cycle , medicine , biology , cancer , in vitro , chemotherapy , biochemistry , human breast , genetics
The aims of this study were to investigate the synergistic anticancer effects of resveratrol with doxorubicin against human breast cancer cell lines. In this study, the doxorubicin‐resistance MCF‐7 (MCF‐7/ADR) and MDA‐MB‐231 cells were treated with resveratrol and doxorubicin, alone or in combination, and we examined cell viability, cell cycle, apoptosis, migration and invasion. Treatment with doxorubicin 1 μM for 24 hr had no effect on the cell viability of MCF‐7/ADR and MDA‐MB‐231 cells. However, combination of doxorubicin and resveratrol significantly reduced viability of MCF‐7/ADR and MDA‐MB‐231 cells, respectively. Although MCF‐7/ADR and MDA‐MB‐231 cells are relatively resistant to the doxorubicin, resveratrol improved the doxorubicin‐induced cytotoxicity in both cell lines. Taken together, combination treatment with resveratrol and doxorubicin decreased MCF‐7/ADR and MDA‐MB‐231 cells migration up to 60% and 80%, respectively, as compared to doxorubicin treatment alone. Similar to migration assay, there was significant reduced the number of invaded cells in assay using Matrigel‐coated chambers. To determine the pathway of anti‐invasive effects, the expression levels of genes involved in migration and invasion were examined in both cell lines. The MMP‐2, MMP‐9 and plasminogen activator (u‐PA) expression levels were significantly decreased following combination treatment. In addition, the expression levels of TIMPs and RECK were markedly increased in case of combination treatment in both cell lines. In conclusion, these findings suggest that resveratrol might be used as a synergistic agent in the treatment of doxorubicin‐resistance breast cancer.