Antitumor bystander effect induced by radiation-inducible target gene therapy combined with α particle irradiation

In this work, we investigated the bystander effect of the tumor and normal cells surrounding the target region caused by radiation-inducible target gene therapy combined with α-particle irradiation. The receptor tumor cell A549 and normal cell MRC-5 were co-cultured with the donor cells irradiated to 0.5 Gy or the non-irradiated donor cells, and their survival and apoptosis fractions were evaluated. The results showed that the combined treatment of Ad-ET and α particle irradiation could induce synergistic antitumor effect on A549 tumor cell, and the survival fraction of receptor cells co-cultured with the irradiated cells decreased by 6%, compared with receptor cells co-cultured with non-irradiated cells, and the apoptosis fraction increased in the same circumstance, but no difference was observed with the normal cells. This study demonstrates that Ad-ET combined with α-particle irradiation can significantly cause the bystander effect on neighboring tumor cells by inhibiting cell growth and inducing apoptosis, without obvious toxicity to normal cells. This suggests that combining radiation-inducible TRAIL gene therapy and irradiation may improve tumor treatment efficacy by specifically targeting tumor cells and even involving the neighboring tumor cells.