title: Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells.
abstract: 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.
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Fang-bo
authors.initials: FB
authors.lastname: Cui
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Ru-Tian
authors.initials: RT
authors.lastname: Li
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Pu-yuan
authors.initials: PY
authors.lastname: Wu
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Yu
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Hu
authors.affiliation: Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Feng-lei
authors.initials: FL
authors.lastname: Wu
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Jiang
authors.affiliation: Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Guo-feng
authors.initials: GF
authors.lastname: Yue
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qian
authors.affiliation: Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xi-Qun
authors.initials: XQ
authors.lastname: Jiang
authors.affiliation: The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, People's Republic of China.
authors.forename: Bao-Rui
authors.initials: BR
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D029968:Escherichia coli Proteins; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000008:administration & dosage / Q000737:chemistry / Q000706:statistics & numerical data; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*
chemical_list: D029968:Escherichia coli Proteins; D053769:Nanocapsules; D010455:Peptides; D011091:Polyesters; D011838:Radiation-Sensitizing Agents; C065100:TraU protein, E coli; C502908:poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol); D011092:Polyethylene Glycols; D018093:Gelatinases
keywords: cancer stem cell-like properties; gastric cancer; gelatinase-stimuli nanoparticles; miR-200c; radiosensitizer