Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis  

作　　者：Zu-Gui Tang Tie-Mei Chen Yi Lu Zhe Wang Xi-Cheng Wang Yi Kong 

机构地区：[1]Department of Oncology,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510080,Guangdong Province,China [2]Faculty of Pharmaceutical Sciences,Shenzhen University of Advanced Technology,Shenzhen 518000,Guangdong Province,China [3]Guangdong Pharmaceutical University,Guangzhou 510006,Guangdong Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第9期4006-4013,共8页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：Guangdong Basic and Applied Basic Research Foundation,No.2019A1515011609;Project of Educational Commission of Guangdong Province of China,No.2018KQNCX124;Guangzhou Science and Technology Key Point Project,No.202103000041.

摘　　要：BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.

关 键 词：Mesenchymal stem cells EXOSOMES Extracellular vesicles GEMCITABINE Pancreatic cancer Drug delivery 

分 类 号：R735[医药卫生—肿瘤]