Abstract:

Objective   To study effects of bortezomib, a ubiquitin-proteasome pathway inhibitor with cytotoxic activity in multiple myeloma in vitro and vivo, alone and in combination with epirubicin on biological characteristics of breast cancer cells. Methods   Michigan Cancer Foundation-7(MCF-7) human breast cancer cell lines were cultured with bortezmib (in concentrations of 0.01, 0.10, 1.00, 5.00 and 10.00μg/mL) alone or plus epitubicin (in concentrations of 0.05, 0.25, 0.50, 1.00 and 5.00μg/mL). Effects of bortezomib and epirubicin on the proliferation and viability of breast cancer cells were studied by the MTT assay. MCF-7 cells were cultured with 0.10μg/mL of bortezomib+0.50μg/mL of epirubicin for 24, 48 and 72hours. The cells stained with propidium iodide were detected for cell cycle analysis. Results   Bortezomib inhibited cell proliferation to some extent, without showing a dose-or time-dependent manner, and it stopped the cell cycle at the G2/M period. Epirubicin significantly inhibited  proliferation of MCF-7 human breast cancer cells in a dose- and time-dependent manner, arresting the cell cycle at the S period. Combination of bortezomib and epirubicin could inhibit proliferation of MCF-7 cells at lower concentrations and shorter time, indicating their synergistic effect. Conclusion   Bortezomib and epirubicin have a synergistic effect over the inhibition of MCF-7 human breast cancer cells. The research shows that the dose of epirubicin can be decreased and its sensitivity can be increased if it is applied with bortezomib, thereby enhancing chemotherapeutic effects and reducing adverse effects of the drugs.

Key words: Breast neoplasms; Bortezomib; Epirubicin; MCF-7 cells; Apoptosis