Ann Surg Treat Res.  2015 Feb;88(2):55-62. 10.4174/astr.2015.88.2.55.

Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7

• Park SO
• Yoo YB
• Kim YH
• Baek KJ
• Yang JH
• Choi PC
• Lee JH
• Lee KR
• Park KS

• KMID: 1804121
• DOI: http://doi.org/10.4174/astr.2015.88.2.55

Abstract

PURPOSE
The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines.
METHODS
Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1microM, or 10microM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated.
RESULTS
In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10microM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group.
CONCLUSION
Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

Keyword

Breast neoplasms; Selenium; Docetaxel; Combination drug therapy

MeSH Terms

Apoptosis
Breast Neoplasms*
Cell Cycle
Cell Cycle Checkpoints
Cell Line*
Cell Proliferation
Drug Therapy
Drug Therapy, Combination
Humans
MCF-7 Cells
Selenium*
Selenium

Figure

• 

  Fig. 1 Cell growth after combined treatment of docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM in the MDA-MB-231 cell line (A) and the MCF-7 cell line (B). Cells were stained with trypan blue to determine cell viability and were quantified using a hemocytometer. Relative cell growth rates are shown as percent survival versus indicated cells after treatment with the drug at different concentrations. The data represent the means of at least three independent experiments and the corresponding standard errors. *P-value less than 0.05.

• 

  Fig. 2 Normalized isobologram for selenium and docetaxel in the MDA-MB-231 (A) and MCF-7 (B) cell lines. Diagonal experimental combination data points, represented by dots located lower left, on the diagonal line, or upper right, indicate synergism, additivity, and antagonism, respectively. Fractional affected-combination index (Fa-CI) plot in combination index analysis in the MDA-MB-231 (C) and MCF-7 (D) cell lines. Combination index values <1, =1, or >1 indicate synergism, additivity, and antagonism, respectively.

• 

  Fig. 3 Apoptosis after combined treatment with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM in the MDA-MB-231 cell line (A) and the MCF-7 cell line (B). All cells were stained with fluorescein isothiocyanate (FITC) conjugated Annexin V in a buffer containing propidium iodide and were analyzed using flow cytometry. For each treatment, the percentage of viable cells is shown in the lower left quadrant, for which both Annexin V and propidium iodide levels are low. Data from a representative experiment (from a total of three) are shown.

• 

  Fig. 4 Cell cycle analysis after combined treatment with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM in the MDA-MB-231 cell line (A) and the MCF-7 cell line (B). The percentage of cells at each stage of the cell cycle was analyzed using flow cytometry after DNA staining with propidium iodide. Data from a representative experiment (from a total of three) are shown.

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