Radiosensitizing effects of arsenic trioxide on MCF-7 human breast cancer cells exposed to 89strontium chloride

摘要

The aim of this study was to investigate the radiosensitizing effects of arsenic trioxide (As 2O 3) on MCF-7 human breast cancer cells irradiated with 89strontium chloride ( 89SrCl 2). The 50% inhibitory concentration (IC 50) was calculated from results of an MTT assay. The concentration of As 2O 3 less than 20% IC 50 was selected for subsequent experiments. Cells were treated with As 2O 3 and 89SrCl 2. Morphological changes of cells were observed under an inverted microscope. The radiosensitivity enhancing ratio (SER) was computed based on a clone formation assay. Cell cycle distribution and apoptosis were measured by flow cytometry (FCM). Expression of Bcl-2 and Bax at both the mRNA and protein levels was assessed by RT-PCR and western blotting. The IC 50 of As 2O 3 at 24 h was 11.7 μM. Doses of As 2O 3 (1 and 2 μM) were used in combination treatments and SER values were 1.25 and 1.79, respectively. As 2O 3 significantly suppressed cell growth, caused G 2/M arrest, enhanced cell death and apoptosis induced by 89SrCl 2and decreased expression of the Bcl-2 gene. Since expression of Bax was unchanged following treatment, As 2O 3 effectively reduced the Bcl-2/Bax ratio. As 2O 3 (1-2 μM) enhances the cytotoxic effects of 89SrCl 2 on the MCF-7 human breast cancer cell line by inducing G 2 phase delay and promoting apoptosis through the reduction of the Bcl-2/Bax ratio.