@article {KIM2885, author = {SEO YUN KIM and EUN-HUI JEONG and TAE-GUL LEE and HYE-RYOUN KIM and CHEOL HYEON KIM}, title = {The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells}, volume = {41}, number = {6}, pages = {2885--2894}, year = {2021}, doi = {10.21873/anticanres.15070}, publisher = {International Institute of Anticancer Research}, abstract = {Background/Aim: We evaluated the radiosensitizing effect of the combination treatment of trametinib, a MEK inhibitor, and temsirolimus, an mTOR inhibitor, on non-small-cell lung carcinoma (NSCLC) cells. Materials and Methods: The effects of combining trametinib and temsirolimus with radiation in NSCLC cell lines were evaluated using clonogenic survival and apoptosis assays. DNA double-strand breaks and cell cycle distribution were analyzed using flow cytometry. Tumor volume was measured to determine the radiosensitivity in lung cancer xenograft models. Results: Exposure of lung cancer cells to a combination of trametinib and temsirolimus reduced clonogenic survival and promoted radiation-induced apoptosis. Combined inhibition of MEK and mTOR induced prolonged expression of γH2AX after irradiation and resulted in prolonged G2/M cell cycle arrest after irradiation in A549 cells. In vivo studies revealed that co-administration of the drugs sensitizes lung cancer xenografts to radiotherapy. Conclusion: The combination of trametinib and temsirolimus can enhance lung cancer radiosensitivity in vitro and in vivo.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/41/6/2885}, eprint = {https://ar.iiarjournals.org/content/41/6/2885.full.pdf}, journal = {Anticancer Research} }