Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Ins...

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Autores principales:	Cui FB, Liu Q, Li RT, Shen J, Wu PY, Yu LX, Hu WJ, Wu FL, Jiang CP, Yue GF, Qian XP, Jiang XQ, Liu BR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/37a7935be4b14dd9b4a64c3a8eee8bbc
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spelling	oai:doaj.org-article:37a7935be4b14dd9b4a64c3a8eee8bbc2021-12-02T03:11:30ZEnhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells1178-2013https://doaj.org/article/37a7935be4b14dd9b4a64c3a8eee8bbc2014-05-01T00:00:00Zhttp://www.dovepress.com/enhancement-of-radiotherapy-efficacy-by-mir-200c-loaded-gelatinase-sti-a16812https://doaj.org/toc/1178-2013 Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC)-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25), but only slightly in GES-1 cells (1.06). In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation.Keywords: radiosensitizer, miR-200c, gelatinase-stimuli nanoparticles, cancer stem cell-like properties, gastric cancerCui FBLiu QLi RTShen JWu PYYu LXHu WJWu FLJiang CPYue GFQian XPJiang XQLiu BRDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 2345-2358 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Cui FB Liu Q Li RT Shen J Wu PY Yu LX Hu WJ Wu FL Jiang CP Yue GF Qian XP Jiang XQ Liu BR Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
description	Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC)-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25), but only slightly in GES-1 cells (1.06). In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation.Keywords: radiosensitizer, miR-200c, gelatinase-stimuli nanoparticles, cancer stem cell-like properties, gastric cancer
format	article
author	Cui FB Liu Q Li RT Shen J Wu PY Yu LX Hu WJ Wu FL Jiang CP Yue GF Qian XP Jiang XQ Liu BR
author_facet	Cui FB Liu Q Li RT Shen J Wu PY Yu LX Hu WJ Wu FL Jiang CP Yue GF Qian XP Jiang XQ Liu BR
author_sort	Cui FB
title	Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
title_short	Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
title_full	Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
title_fullStr	Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
title_full_unstemmed	Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells
title_sort	enhancement of radiotherapy efficacy by mir-200c-loaded gelatinase-stimuli peg-pep-pcl nanoparticles in gastric cancer cells
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/37a7935be4b14dd9b4a64c3a8eee8bbc
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Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

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