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Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610438/ https://www.ncbi.nlm.nih.gov/pubmed/23662044 http://dx.doi.org/10.2147/DDDT.S42390 |
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author | Dai, Zhi-Jun Gao, Jie Kang, Hua-Feng Ma, Yu-Guang Ma, Xiao-Bin Lu, Wang-Feng Lin, Shuai Ma, Hong-Bing Wang, Xi-Jing Wu, Wen-Ying |
author_facet | Dai, Zhi-Jun Gao, Jie Kang, Hua-Feng Ma, Yu-Guang Ma, Xiao-Bin Lu, Wang-Feng Lin, Shuai Ma, Hong-Bing Wang, Xi-Jing Wu, Wen-Ying |
author_sort | Dai, Zhi-Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3610438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36104382013-05-09 Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells Dai, Zhi-Jun Gao, Jie Kang, Hua-Feng Ma, Yu-Guang Ma, Xiao-Bin Lu, Wang-Feng Lin, Shuai Ma, Hong-Bing Wang, Xi-Jing Wu, Wen-Ying Drug Des Devel Ther Original Research 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. Dove Medical Press 2013-03-19 /pmc/articles/PMC3610438/ /pubmed/23662044 http://dx.doi.org/10.2147/DDDT.S42390 Text en © 2013 Dai et al, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Dai, Zhi-Jun Gao, Jie Kang, Hua-Feng Ma, Yu-Guang Ma, Xiao-Bin Lu, Wang-Feng Lin, Shuai Ma, Hong-Bing Wang, Xi-Jing Wu, Wen-Ying Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title | Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title_full | Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title_fullStr | Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title_full_unstemmed | Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title_short | Targeted inhibition of mammalian target of rapamycin (mTOR) enhances radiosensitivity in pancreatic carcinoma cells |
title_sort | targeted inhibition of mammalian target of rapamycin (mtor) enhances radiosensitivity in pancreatic carcinoma cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3610438/ https://www.ncbi.nlm.nih.gov/pubmed/23662044 http://dx.doi.org/10.2147/DDDT.S42390 |
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