title: Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells.
abstract: The mammalian target of rapamycin (mTOR) is a protein kinase that regulates protein translation, cell growth, and apoptosis. Rapamycin (RPM), a specific inhibitor of mTOR, exhibits potent and broad in vitro and in vivo antitumor activity against leukemia, breast cancer, and melanoma. Recent studies showing that RPM sensitizes cancers to chemotherapy and radiation therapy have attracted considerable attention. This study aimed to examine the radiosensitizing effect of RPM in vitro, as well as its mechanism of action. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay showed that 10 nmol/L to 15 nmol/L of RPM had a radiosensitizing effects on pancreatic carcinoma cells in vitro. Furthermore, a low dose of RPM induced autophagy and reduced the number of S-phase cells. When radiation treatment was combined with RPM, the PC-2 cell cycle arrested in the G2/M phase of the cell cycle. Complementary DNA (cDNA) microarray and reverse transcription polymerase chain reaction (RT-PCR) revealed that the expression of DDB1, RAD51, and XRCC5 were downregulated, whereas the expression of PCNA and ABCC4 were upregulated in PC-2 cells. The results demonstrated that RPM effectively enhanced the radiosensitivity of pancreatic carcinoma cells.
authors: Department of Oncology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, People's Republic of China. dzj0911@126.com
authors: Zhi-Jun
authors: ZJ
authors: Dai
authors: Jie
authors: J
authors: Gao
authors: Hua-Feng
authors: HF
authors: Kang
authors: Yu-Guang
authors: YG
authors: Ma
authors: Xiao-Bin
authors: XB
authors: Ma
authors: Wang-Feng
authors: WF
authors: Lu
authors: Shuai
authors: S
authors: Lin
authors: Hong-Bing
authors: HB
authors: Ma
authors: Xi-Jing
authors: XJ
authors: Wang
authors: Wen-Ying
authors: WY
authors: Wu
mesh_terms: D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: mTOR; pancreatic carcinoma; radiation; rapamycin
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