Sustained enhancement of liposome-mediated gene delivery and gene expression in human breast tumour cells by ionizing radiation

Abstract

Purpose: To investigate whether irradiation improves the delivery and expression of liposome-DNA complexes in human breast tumour cells. Materials and methods: MDA-MB231 and MCF-7 human breast tumour cells were transfected with a liposomal SV40-luciferase complex and irradiated immediately after, at 24h after or 24h prior to transfection and in the presence or absence of serum. The amount of luciferase plasmid in the cell was evaluated after extraction by the Hirt procedure, while luciferase expression was measured using a luminescence assay. Results: Ionizing radiation enhanced the liposome-mediated delivery and expression of the SV40-luciferase transgene in MDAMB231 breast tumour cells both in the absence and presence of serum as well as in MCF-7 breast tumour cells. Improved transgene delivery and expression was observed at a clinically relevant dose of 2Gy, and was dose-dependent over a dose range of 2-10Gy. The effects of irradiation on transgene expression were observed with irradiation immediately prior to exposure of the cells to the liposome-transgene complex, with irradiation up to 24h before or up to 24h after initiation of exposure. Conclusions: Irradiation at 24h prior to exposure of breast tumour cells to the liposome-transgene complex appears to be the optimal approach for enhancing transgene delivery and expression. These findings suggest that ionizing radiation could promote the utility of gene therapy in the treatment of breast cancer.