title: Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion.
abstract: Glioblastoma (GBM) remains as the most common and aggressive brain tumor. The survival of GBM has been linked to the aberrant activation of swelling-induced chloride current ICl,swell. In this study, we investigated the effects of ICl,swellon cell viability, proliferation, and migration in the human GBM cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. First, we showed that the specific inhibitor of ICl,swell, DCPIB, potently reduced the ICl,swellin U87 cells. Next, in both U87 and U251 cells, we found that DCPIB reduced GBM viability, proliferation, colony formation, migration, and invasion. In addition, our Western immunoblot assay showed that DCPIB-treated U251 cells had a reduction in JAK2, STAT3, and Akt phosphorylation, thus, suggesting that DCPIB potentially suppresses GBM functions through inhibition of the JAK2/STAT3 and PI3K/Akt signaling pathways. Therefore, the ICl,swellmay be a potential drug target for GBM.
authors.affiliation: Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.|Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.affiliation: Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Wenliang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
authors.affiliation: Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, Canada.|Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada.|Departments of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Hong-Shuo
authors.identifier: http://orcid.org/0000-0001-5142-1874
authors.initials: HS
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism; D008564:Membrane Potentials; D009361:Neoplasm Invasiveness; D018408:Patch-Clamp Techniques; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: C443139:4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-one-5-yl)oxybutyric acid; D000970:Antineoplastic Agents; D018118:Chloride Channels; D002712:Chlorides; D003517:Cyclopentanes; D007189:Indans; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D058539:Phosphatidylinositol 3-Kinase; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt
keywords: GBM; U251; U87; glioblastoma; invasion; migration; proliferation; swelling-induced chloride current