Effect of intermittent low-dose irradiation on the radiotherapy efficiency for MDA-MB-231 human breast adenocarcinoma cell line
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Despite the fact that high-dose radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that it might confer radioresistance. Hyper-radiosensitivity (HRS) is one of the important biological effects of low-dose ionizing radiation (LDIR) in mammalian cell lines. LDIR is considered as a promising assistant method of clinical cancer therapy. The purpose of this study was to evaluate the efficiency of intermittent LDIR followed by a high-dose radiation therapeutic approach compared with the conventional high-dose radiotherapy in the breast cancer MDA-MB-231 cell line.
Materials and methods
MDA-MB-231 cells were divided into four experimental groups—intermittent LDIR group: cells were irradiated for 10 fractions with a dose of 30 mGy at each time (interval 24 h) followed by 2 Gy, single LDIR group: cells have accepted a dose of 300 mGy LDIR and after 24 h a high dose of 2 Gy, high-dose ionizing radiation (HDIR) group: cells were exposed to a single high dose of 2 Gy, and control group.
MTT and flow cytometry assay were used for cell proliferation and apoptosis after 24 h of the last irradiation dose (2 Gy). Also, we examined p21 and cespase3 gene expression by RT-qPCR. We observed that intermittent LDIR significantly increased the killing effect of radiotherapy (viability, 71.95 + 1.25%) (P < 0.01). The apoptosis is proposed to increase up to 32.55 + 0.07% in the intermittent LDIR that was markedly higher than those of other groups (P < 0.01). Caspase3 gene expression in this group was the highest (5.2-fold), 4.26-fold and 1.42-fold in single LDIR and HDIR, respectively. It was observed that the intermittent LDIR potentially decreases p21 expression in comparison with the challenge dose of 2 Gy (0.681-fold).
LDIR may result in HRS through a concurrent increase of apoptosis and a significant decrease in cell viability. The therapeutic effects of this approach should be further investigated in animal models.
KeywordsLow-dose irradiation Breast adenocarcinoma Radiotherapy Hyper-radiosensitivity (HRS)
High-dose ionizing radiation
Low-dose ionizing radiation
- Int. L + H
Intermittent LDIR followed by HDIR
- Single L + H
Single LDIR followed by HDIR
Compliance with ethical standards
This study was funded by the Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran (Grant No.: U–96124).
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants performed by any of the authors.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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