title: Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.
abstract: Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.|Department of Neurosurgery, The Second Clinical College of Fujian Medical University, Quanzhou, Fujian Province, China.
authors.forename: Xian-Bin
authors.initials: XB
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Mao-Hua
authors.initials: MH
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Chen-Ran
authors.initials: CR
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Hong-Kang
authors.initials: HK
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Cheng-Yin
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
authors.forename: Jue-Yu
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of the Ministry of Education, School of Electronic Information and Electronic Engineering, Institute of Nano Biomedicine and Engineering, Shanghai Jiaotong University, Shanghai, China. weilinjin@sjtu.edu.cn.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China. huguohan@hotmail.com.
authors.forename: Guo-Han
authors.initials: GH
authors.lastname: Hu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000032:analysis; D010643:Phenoxybenzamine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010643:Phenoxybenzamine
keywords: Akt; Glioma; LINGO-1; Phenoxybenzamine hydrochloride; TrkB