| 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 Name | Affiliation | E-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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