RT Journal Article
SR Electronic
T1 The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2885
OP 2894
DO 10.21873/anticanres.15070
VO 41
IS 6
A1 SEO YUN KIM
A1 EUN-HUI JEONG
A1 TAE-GUL LEE
A1 HYE-RYOUN KIM
A1 CHEOL HYEON KIM
YR 2021
UL http://ar.iiarjournals.org/content/41/6/2885.abstract
AB 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.