title: Destruction of vasculogenic mimicry channels by targeting epirubicin plus celecoxib liposomes in treatment of brain glioma.
abstract: The efficacy of chemotherapy for brain glioma is restricted by the blood-brain barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the treatment of intracranial glioma-bearing nude mice. Therefore, targeting epirubicin plus celecoxib liposomes could be a potential nanostructured formulation to treat gliomas and destroy their VM channels.
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China; Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, People's Republic of China.
authors.forename: Rui-Jun
authors.initials: RJ
authors.lastname: Ju
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Mu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Xie
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Jia-Shuan
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Hu
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Wan-Liang
authors.initials: WL
authors.lastname: Lu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053181:Caspase 8 / Q000378:metabolism; D000068579:Celecoxib / Q000008:administration & dosage; D045744:Cell Line, Tumor; D015251:Epirubicin / Q000008:administration & dosage; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local
chemical_list: D008081:Liposomes; D015251:Epirubicin; D053181:Caspase 8; D000068579:Celecoxib
keywords: brain glioma; celecoxib; epirubicin; targeting liposomes; vasculogenic mimicry channels