Inhibition of xenograft human glioma tumor growth by lentivirus-mediated gene transfer of alphastatin

Che,Hongmin; Song,Jianrong; Guo,Shiwen; Wang,Weiwen; Gao,Guodong

doi:10.3892/or.2012.2187

Inhibition of xenograft human glioma tumor growth by lentivirus-mediated gene transfer of alphastatin

Authors:
- Hongmin Che
- Jianrong Song
- Shiwen Guo
- Weiwen Wang
- Guodong Gao
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Affiliations: Department of Neurosurgery, The Second Affiliated Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China, Department of Neurosurgery, Baoji Municipal Central Hospital, Baoji, Shannxi 721008, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710061, P.R. China
Published online on: December 14, 2012 https://doi.org/10.3892/or.2012.2187
Pages: 1101-1107

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Abstract

Angiogenesis is crucial for the development and metastasis of human brain glioma. Based on our previous successful construction of a lentivirus-mediated alphastatin (an endogenous angiogenesis inhibitor) gene transfer system and our findings that alphastatin exhibited potent inhibitory effects on the migration and differentiation of human umbilical vein endothelial cell lines (HUVECs) induced by vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro, here, we investigated the effect of using lentiviral vectors to overexpress alphastatin in human glioma cells to show whether sustained long-term expression of alphastatin diminishes tumor growth in a xenograft glioma model. We found that the transduced glioma cells sustainedly secreted alphastatin, which did not affect the proliferative ability of the glioma cells. Furthermore, tumor xenografts treated with the recombinant lentivirus were significantly smaller compared to the control xenografts and vascularity within the treated tumors was evidently decreased. Our data suggest that stable expression of alphastatin inhibits human glioma growth by inhibiting angiogenesis, with a probable mechanism of suppressing the turnover of VE-cadherin membrane molecules.

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