title: miRNA-218-loaded carboxymethyl chitosan - Tocopherol nanoparticle to suppress the proliferation of gastrointestinal stromal tumor growth.
abstract: Gastrointestinal stromal tumors (GIST) are one of the most common forms of mesenchymal cancers of the gastrointestinal tract. Although chemotherapeutic drugs inhibited the proliferation of GIST, however, sizable proportion of people developed resistance and therefore difficult to treat. In the present study, O-carboxymethyl chitosan (OCMC)-tocopherol polymer conjugate was synthesized and formulated into stable polymeric nanoparticles. The main aim of present study was to increase the therapeutic efficacy of miR-218 in GIST. The mean size of nanoparticles was ~110nm with a spherical shape. The miR-218 NP has been shown inhibit the cell proliferation and exhibited a superior cell apoptosis. The miR-218 NP inhibited the cell invasion and promoted the apoptosis of GIST cancer cells. In the present study, we have successfully showed that KIT1 is the target gene of miR-218 as shown by the luciferase reporter assay. These findings collectively suggest the miR-218 loaded nanoparticle by virtue of effective transfection could act as a tumor suppressor miRNA in the treatment of GIST.
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tu
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Zi-Zhen
authors.initials: ZZ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Tang
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China.
authors.forename: Ye-Qian
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China. Electronic address: caohui10281@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: State Key Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200240, PR China. Electronic address: zhangzhiganggz@hotmail.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D024505:Tocopherols / Q000737:chemistry*
chemical_list: D035683:MicroRNAs; C514968:carboxymethyl-chitosan; D048271:Chitosan; D019009:Proto-Oncogene Proteins c-kit; D024505:Tocopherols
keywords: Antitumor; Apoptosis; Gastrointestinal tumors; Nanoparticles; miRNA-218