Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells

  • Tumour Biol. 2016 Mar;37(3):2901-8. doi: 10.1007/s13277-015-4102-y.
Xian-Bin Lin  1  2 ,  Lei Jiang  1 ,  Mao-Hua Ding  1 ,  Zhen-Hua Chen  1 ,  Yi Bao  3 ,  Yi Chen  1 ,  Wei Sun  1 ,  Chen-Ran Zhang  1 ,  Hong-Kang Hu  1 ,  Zhen Cai  1 ,  Cheng-Yin Lu  1 ,  Jue-Yu Zhou  4 ,  Jun Qian  1 ,  Xiao-Jun Wu  1 ,  Wei-Lin Jin  5 ,  Guo-Han Hu  6
Affiliations
  • 1. Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China.
  • 2. Department of Neurosurgery, The Second Clinical College of Fujian Medical University, Quanzhou, Fujian Province, China.
  • 3. Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
  • 4. Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
  • 5. 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. [email protected].
  • 6. Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, No.415 FengYang Road, Shanghai, China. [email protected].
PMID: 26409450 DOI: 10.1007/s13277-015-4102-y
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.

Keywords
Akt; Glioma; LINGO-1; Phenoxybenzamine hydrochloride; TrkB.
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