Inhibition of histamine receptor 3 suppresses glioblastoma tumor growth, invasion, and epithelial-to-mesenchymal transition.

摘要: // Jia-Ji Lin 1, * , Tian-Zhi Zhao 2, Wen-Ke Cai 3, Yong-Xiang Yang 1 Chao Sun Zhuo Zhang Yu-Qiao Xu 4 Ting Chang Zhu-Yi Li Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China 2 Neurosurgery, 3 Cardio-Thoracic Surgery, Kunming General Hospital Chengdu Region, Kunming, Pathology, These authors have contributed equally to this work Correspondence to: Li, e-mail: lizhuyi126@126.com Chang, tdchangting126@126.com Keywords: histamine receptor glioblastoma, epithelial-to-mesenchymal transition, invasion Received: January 25, 2015      Accepted: March 24, Published: April 10, 2015 ABSTRACT Histamine (H3R) is expressed in various tumors and correlated with malignancy tumor proliferation. However, the role H3R epithelial mesenchymal transition (EMT) remains unknown. Here, we explored highly invasive glioblastoma (GBM) U87MG cells. We found that mRNA protein levels were up-regulated GBM glioma cell lines compared normal brain tissue astrocytes. In line, inhibition by siRNA or antagonist ciproxifan (CPX) suppressed proliferation, invasiveness, expression EMT activators (Snail, Slug Twist). addition, markers (E-cadherin ZO-1) was (vimentin N-cadherin) down-regulated vitro vivo a xenograft model. also showed CPX inactivated PI3K/Akt MEK/ERK signaling pathways, while Akt ERK activity antagonists siRNAs agonist ( R )-(α)-(-)- methylhistamine dihydrobromide (RAMH) mediated reorganization cadherin-household. conclusion, overexpression associated progression. Inhibition leads inactivating pathways gliomas.