title: Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.
abstract: 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.
authors.affiliation: a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China.|b National Engineering Research Center of Microbial Medicine, New Drug Research and Development Centre of North China Pharmaceutical Group Corporation, Hebei, Shijiazhuang 050015, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: b National Engineering Research Center of Microbial Medicine, New Drug Research and Development Centre of North China Pharmaceutical Group Corporation, Hebei, Shijiazhuang 050015, China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Wang
authors.affiliation: c School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Nan
authors.affiliation: a School of Pharmaceutical Science and Technology, Tianjin University, Nankai District, Tianjin 300072, China.
authors.forename: He
authors.initials: H
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D006657:Histones / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C468783:H2AX protein, human; D006657:Histones; D011838:Radiation-Sensitizing Agents; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: cancer pulmonaire; lung cancer; mTOR (« mammalian target of rapamycin »); mammalian target of rapamycin (mTOR); radiation; radiosensibilité; radiosensitivity; rapamycin; rapamycine