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Biochem Cell Biol ; 94(3): 213-20, 2016 06.
Article in English | MEDLINE | ID: mdl-26999331

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.


Subject(s)
Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Lung/radiation effects , Radiation-Sensitizing Agents/pharmacology , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/antagonists & inhibitors , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Line , Cell Line, Tumor , Comet Assay , DNA Damage/drug effects , DNA Damage/genetics , DNA Damage/radiation effects , Gamma Rays , Histones/metabolism , Humans , Lung/cytology , Lung Neoplasms/genetics , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , TOR Serine-Threonine Kinases/metabolism
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