PMID- 26999331 OWN - NLM STAT- MEDLINE DCOM- 20170620 LR - 20211204 IS - 1208-6002 (Electronic) IS - 0829-8211 (Linking) VI - 94 IP - 3 DP - 2016 Jun TI - Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation. PG - 213-20 LID - 10.1139/bcb-2015-0139 [doi] AB - Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation. FAU - Zheng, Hang AU - Zheng H AD - a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China. FAU - Wang, Miao AU - Wang M AD - a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China. AD - b National Engineering Research Center of Microbial Medicine, New Drug Research and Development Centre of North China Pharmaceutical Group Corporation, Hebei, Shijiazhuang 050015, China. FAU - Wu, Jing AU - Wu J AD - a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China. FAU - Wang, Zhi-Ming AU - Wang ZM AD - b National Engineering Research Center of Microbial Medicine, New Drug Research and Development Centre of North China Pharmaceutical Group Corporation, Hebei, Shijiazhuang 050015, China. FAU - Nan, Hai-Jun AU - Nan HJ AD - c School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Sun, He AU - Sun H AD - a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China. LA - eng PT - Journal Article DEP - 20160118 PL - Canada TA - Biochem Cell Biol JT - Biochemistry and cell biology = Biochimie et biologie cellulaire JID - 8606068 RN - 0 (H2AX protein, human) RN - 0 (Histones) RN - 0 (Radiation-Sensitizing Agents) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Apoptosis/drug effects/radiation effects MH - Cell Line MH - Cell Line, Tumor MH - Comet Assay MH - DNA Damage/drug effects/genetics/radiation effects MH - Gamma Rays MH - Histones/metabolism MH - Humans MH - Lung/cytology/*radiation effects MH - Lung Neoplasms/*drug therapy/genetics/*radiotherapy MH - Radiation-Sensitizing Agents/*pharmacology MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism OTO - NOTNLM OT - cancer pulmonaire OT - lung cancer OT - mTOR (<< mammalian target of rapamycin >>) OT - mammalian target of rapamycin (mTOR) OT - radiation OT - radiosensibilite OT - radiosensitivity OT - rapamycin OT - rapamycine EDAT- 2016/03/22 06:00 MHDA- 2017/06/21 06:00 CRDT- 2016/03/22 06:00 PHST- 2016/03/22 06:00 [entrez] PHST- 2016/03/22 06:00 [pubmed] PHST- 2017/06/21 06:00 [medline] AID - 10.1139/bcb-2015-0139 [doi] PST - ppublish SO - Biochem Cell Biol. 2016 Jun;94(3):213-20. doi: 10.1139/bcb-2015-0139. Epub 2016 Jan 18.