Dihydroartemisinin increases radiosensitivity of A549 lung cancer cells

Background: Radiotherapy is the gold standard in the treatment of lung cancer. However, the radiosensitization of cancerous cells requires further improvement. Here, we investigated the effect of dihydroartemisinin (DHA) on the radiosensitization of non-small cell lung cancer (NSCLC) cells. Methods: Cell proliferation and cell cycle assays were carried out using A549 cells exposed to DHA. The effect of DHA on the radiosensitization of cells was investigated by clonogenic cell survival assay and apoptosis assay. Polymerase chain reaction and western blotting were used to quantify GSK-3β level.  Results: DHA significantly inhibited cell proliferation from 24 to 96 h. Cells treated with DHA had a significantly decrease G1 phase but significantly increase S and G2/M phases compared with untreated and vehicle-treated cells. The number of viable DHA-treated cell colonies was significantly lower than that of untreated or vehicle-treated cells. The percentage of early apoptotic and necrotic cells was significantly higher for cells exposed to DHA and irradiation. GSK-3β expression was significantly higher in cells exposed to DHA and irradiation than that in untreated cells, indicating that DHA may enhances the radiosensitization of cells through the activation of GSK-3β. Conclusions: Our results demonstrate that DHA can increase the radiosensitivity of A549 cells, suggested its potential use to sensitize tumors to radiation therapy in NSCLC. The expressions of GSK-3β were induced by DHA in cells exposed to irradiation, indicating GSK-3β may paly important role in the radiosensitization mechanism of DHA.