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Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy

Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechani...

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Autores principales: Dai, Zhi-Jun, Gao, Jie, Ma, Xiao-Bin, Kang, Hua-Feng, Wang, Bao-Feng, Lu, Wang-Feng, Lin, Shuai, Wang, Xi-Jing, Wu, Wen-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565263/
https://www.ncbi.nlm.nih.gov/pubmed/23344033
http://dx.doi.org/10.3390/ijms14010273
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author Dai, Zhi-Jun
Gao, Jie
Ma, Xiao-Bin
Kang, Hua-Feng
Wang, Bao-Feng
Lu, Wang-Feng
Lin, Shuai
Wang, Xi-Jing
Wu, Wen-Ying
author_facet Dai, Zhi-Jun
Gao, Jie
Ma, Xiao-Bin
Kang, Hua-Feng
Wang, Bao-Feng
Lu, Wang-Feng
Lin, Shuai
Wang, Xi-Jing
Wu, Wen-Ying
author_sort Dai, Zhi-Jun
collection PubMed
description Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells.
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spelling pubmed-35652632013-03-13 Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy Dai, Zhi-Jun Gao, Jie Ma, Xiao-Bin Kang, Hua-Feng Wang, Bao-Feng Lu, Wang-Feng Lin, Shuai Wang, Xi-Jing Wu, Wen-Ying Int J Mol Sci Article Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells. MDPI 2012-12-21 /pmc/articles/PMC3565263/ /pubmed/23344033 http://dx.doi.org/10.3390/ijms14010273 Text en © 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Dai, Zhi-Jun
Gao, Jie
Ma, Xiao-Bin
Kang, Hua-Feng
Wang, Bao-Feng
Lu, Wang-Feng
Lin, Shuai
Wang, Xi-Jing
Wu, Wen-Ying
Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title_full Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title_fullStr Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title_full_unstemmed Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title_short Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
title_sort antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565263/
https://www.ncbi.nlm.nih.gov/pubmed/23344033
http://dx.doi.org/10.3390/ijms14010273
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