Yunyan Luan,Hongwei Xue,Lijian Zhang,Ruyong Yao,Hongsheng Yu. Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in liver cancer xenograft model. Oncol Transl Med, 2014, 13: 572-577.
Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in liver cancer xenograft model
Received:October 28, 2014  Revised:December 04, 2014
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KeyWord:vasculogenic mimicry; H22 hepatoma carcinoma model; grape seed proanthocyanidins; VEGF, EphA2, MMP-2
Author NameAffiliationE-mail
Yunyan Luan The Affiliated Hospital of Qingdao University xiaoluanhai@sina.com 
Hongwei Xue The Affiliated Hospital of Qingdao University  
Lijian Zhang The Affiliated Hospital of Qingdao University  
Ruyong Yao The Affiliated Hospital of Qingdao University  
Hongsheng Yu The Affiliated Hospital of Qingdao University qdhsyu@126.com 
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Abstract:
      Objective: As a novel blood supply pattern, vasculogenic mimicry (VM) has attracted increasingly attention in recent years, which may partly compensate for the absence of feeding and facilitate tumor perfusion. However, anti-angiogenic drugs have little effect on VM. The grape seed proanthocyanidins (GSPs), a kind of promising bioactive phytochemical, has shown anti-carcinogenesis and anti-angiogenic in several tumor models. However, GSPs regulation of VM and its possible mechanisms in a H22 hepatoma carcinoma model remain not clear. The aim of this study was to examine the effects of GSPs on proliferation and VM in a H22 hepatoma carcinoma model and to investigate the underlying mechanism. Methods: Seventy-five mice were divided into the control group and experimental groups treated with different concentration of GSPs. CD34-PAS dual staining was employed to identify the VM structure. The immunohistochemical staining for investigating the expression of VEGF, EphA2 and MMP-2 protein was performed. Results: Treatment of the H22 model with Endostar (4 mg/kg), 50, 100, 200 mg/kg of the GSPs resulted in 6.87%, 17.81%, 27.43%, 53.52% inhibition in tumor growth, respectively. The mean weight of tumors were significantly lower in GSPs (100 mg/kg) and GSPs (200 mg/kg) groups than in the control group (all P < 0.01). Similarly, compared with the control group, the number of VM channels were significantly reduced in GSPs (100 mg/kg) and GSPs (200 mg/kg) groups (all P < 0.01). Immunohistochemistry showed significant decreases in the expression levels of VEGF, EphA2 and MMP-2 protein in GSPs (100 mg/kg) and GSPs (200 mg/kg) groups when compared with control group (all P < 0.001). Conclusion: This is the first report providing evidence that GSPs inhibit the VM structure by regulation of the VEGF/EphA2/MMPs signaling pathway. Therefore, we concluded that GSPs has the potential of being a clinical anti-VM inhibitor.
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