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.

Bystander effects of ionizing radiation: conditioned media from X-ray irradiated MCF-7 cells increases the angiogenic ability of endothelial cells

“…In addition, wound healing assay further confirms the migration ability of HUVECs in that, the percentage of wound healing rate dose-dependently increased at the endpoint of exposure. More recently, it was demonstrated that the CMs collected from irradiated human lung cancer cells enhanced the non-irradiated cells’ migration rate [40]. These results highlight the induction of migration responses of HUVECs against irradiated CMs, however the underlying mechanisms largely remain unknown.…”

Composition of Conditioned Media from Radioresistant and Chemoresistant Cancer Cells Reveals miRNA and Other Secretory Factors Implicated in the Development of Resistance

“…Other studies explored radioresistance induction and showed that CM from previously irradiated cells also showed protective effects in the A549 cells upon additional X-ray exposure, leading to lower apoptotic rates [4]. CM from three types of previously irradiated lung cancer cells facilitated decreased cell death upon irradiation of sensitive cells via increased plasminogen activator inhibitor-1 (PAI-1) that upregulated AKT and ERK1/2 pathways and inhibited caspase-3 activity [5].…”