Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor2 /focal adhesion kinase /Paxillin signaling pathway  

作　　者：WNAG Hui SUN Wei ZHANG Wen-zhong GE Chun-yan ZHANG Jing-tao LIU Zhong-yan FAN Yue-zu 

机构地区：[1]Department of Surgery,Tongji Hospital,Tongji University School of Medicine,Tongji University [2]Department of Surgery,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Tongji University [3]Department of Surgery,Shanghai Pudong New Area People ’s Hospital [4]Department of Oncology,Shanghai Yangpu Geriatric Hospital

出　　处：《外科研究与新技术》2014年第1期64-64,共1页Surgical Research and New Technique

摘　　要：Vasculogenic mimicry(VM)is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors.We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2(EphA2)/focal adhesion kinase(FAK)/Paxillin signaling pathways.In this study,we further investigated the anti-VM activity of norcantharidin(NCTD)as a VM inhibitor for gallbladder cancers and the underlying mechanisms.In vivo and in vitro experiments to determine the effects of NCTD on tumor growth,host survival,VM formation of GBC-SD nude mouse xenografts,and vasculogenic-like networks,malignant phenotypes i.e.,proliferation,apoptosis,invasion and migration of GBC-SD cells.Expression of VM signaling-related markers EphA2,FAK and Paxillin in vivo and in vitro were examined by immunofluorescence,western blotting and real-time polymerase chain reaction(RT-PCR),respectively.The results showed that after treatment with NCTD,GBCSD cells were unable to form VM structures when injecting into nude mouse,growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional(3-D)matrix,proliferation,apoptosis,invasion,migration of GBC-SD cells were affected;and survival time of the xenograft mice was prolonged.Furthermore,expression of EphA2,FAK and Paxillin proteins/mRNAs of the xenografts was downregulated.Thus,we concluded that NCTD has potential antiVM activity against human gallbladder cancers;one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.Vasculogenic mimicry （VM） is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 （EphA2）/focal adhesion kinase （FAK）/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin （NCTD） as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks ,malignant phenotypes i. e. ,proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofiuorescence, western blotting and real-time polymerase chain reaction （RT-PCR）, respectively. The results showed that after treatment with NCTD, GBC- SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional （ 3-D ） matrix, proliferation, apoptosis, invasion, migration of GBC-SD ceils were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti- VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

关 键 词：恶性肿瘤 治疗方法 临床分析 人胆囊癌 

分 类 号：R735.8[医药卫生—肿瘤]