2. National Research Institute of Chinese Medicine, Taipei 11221, Taiwan.
Background: Tamoxifen and Doxorubicin are used alone or in combination to treat breast cancer. Although these drugs have been utilized in combination, the advantage of their combination, in terms of therapeutic efficacy, still remains controversial.
Methods: Cells were treated with Tamoxifen alone and doxorubicin alone or treated with both Tamoxifen and doxorubicin, cell cycle distribution, cell cycle regulatory protein, mRNA, and activity were measured.
Results: This study uses breast cancer cell lines to demonstrate the synergistic interaction between Doxorubicin and Tamoxifen, and to explain the CDK1 and CDK2 expression underlying the synergy. This study demonstrates that the combination of Doxorubicin and Tamoxifen significantly reduces the growth of ER-positive breast cancer cells and that this is driven primarily by the enhanced effect of the decreased protein expression of the CDK1, CDK2 and cyclin D. It is also proposed that selective modification of AKT inactivation, ERK activation probably contributes to the synergistic interaction.
Conclusions: Overall, the findings suggest that a combination of Doxorubicin and Tamoxifen could be effective in the treatment of ER-positive breast cancers, so this combination warrants further investigation.
Keywords: Tamoxifen, doxorubicin, BT483 cells, CDK1, CDK2