PT  - JOURNAL ARTICLE
AU  - SEO YUN KIM
AU  - EUN-HUI JEONG
AU  - TAE-GUL LEE
AU  - HYE-RYOUN KIM
AU  - CHEOL HYEON KIM
TI  - The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells
AID  - 10.21873/anticanres.15070
DP  - 2021 Jun 01
TA  - Anticancer Research
PG  - 2885--2894
VI  - 41
IP  - 6
4099  - http://ar.iiarjournals.org/content/41/6/2885.short
4100  - http://ar.iiarjournals.org/content/41/6/2885.full
SO  - Anticancer Res2021 Jun 01; 41
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.