Effects of irradiated cell conditioned medium on the response of human lung cancer cells to anticancer treatment in vitro

Abstract

Ionizing radiation induces a cellular response not only in the irradiated cells, but also in the neighboring non-irradiated cells, and this effect is known as the radiation-induced bystander effect. The irradiated cells transmit signals to the non-irradiated cells via gap junctions or soluble factors, exerting biological effects on the neighboring non-irradiated cells. In this study, we investigated the effects of irradiated cell conditioned medium (ICCM) on the response of human lung cancer cells (A549 and H1299) to anticancer treatment. First, we analyzed the effects of ICCM on the induction of apoptosis by anticancer treatment (ionizing radiation or gefitinib). Human lung cancer cells were cultured with ICCM from non-irradiated and 8 Gy-irradiated cells and, subsequently, exposed to 8 Gy X-ray. In the A549 cells, the proportion of Annexin V+ apoptotic cells was significantly lower in the cells treated with ICCM from 8 Gy-irradiated cells when compared with that in the cells treated with ICCM from non-irradiated cells (P<0.05), whereas this effect was not observed in the H1299 cells. Furthermore, no significant difference in the proportion of Annexin V+ cells was noted following treatment with gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, between the cells treated with ICCM from non-irradiated cells and those treated with ICCM from the 8 Gy-irradiated cells. We then examined the effects of ICCM on the migration of A549 cells by scratch assay. ICCM from the 8 Gy-irradiated cells enhanced the migration of the 8 Gy-irradiated cells, but not that of the non-irradiated cells. Taken together, these results suggest that cancer cells treated with ICCM exhibit resistance to ionizing radiation in terms of apoptosis and cellular migration, although this phenomenon depends on the cell type.