| Purpose: Two-deoxy-D-glucose (2DG) causes cytotoxicity in the cancer cells by disrupting the
thiol metabolism, and MLN4924 inactivates the SCF E3 ligase and so causes the accumulation of
its substrates which trigger apoptosis and hence might enhance the efficiency of radiotherapy
and overcame on the radioresistance of the cancer cells.
Materials and methods: SKBR3 and MCF-7 breast cancer cells were treated with 500 lM 2DG
and/or MLN4924 (30, 100, 200 and 300 nM), and in combination in the presence and absence of
1, 1.5 and 2 Gy gamma irradiation. The effects of the treatments – 2DG, MLN4924, irradiation
alone and combined – on MCF-7 and SKBR3 cell lines were evaluated by MTT assay, TUNEL
assay, cell death detection, Q-PCR for caspase-3 and Bcl-2 expression analysis, and finally clonogenic
survival assay.
Results: The treatments enhanced the further radio cytotoxicity via inducing the apoptosis cell
signaling gene, caspase-3. The 2DG and MLN4924 treatments could act as a radiosensitizer, especially
on the SKBR3 cells, and further sensitized the cells with a sensitivity enhancement ratio
(SER) of 1.41 and 1.27 in SKBR3 and MCF-7 cells, respectively.
Conclusion: The combined chemo-radiotherapy might improve the breast cancer treatment outcome. |