Recombinant adeno-associated virus-delivered anginex inhibits angiogenesis and growth of HUVECs by regulating the Akt, JNK and NF-κB signaling pathways

Ma,Ke; Wang,Chuying; Geng,Qianqian; Fan,Yangwei; Ning,Jing; Yang,Haixia; Dong,Xuyuan; Dong,Danfeng; Guo,Yuyan; Wei,Xin; Li,Enxiao; Wu,Yinying

doi:10.3892/or.2016.4711

Recombinant adeno-associated virus-delivered anginex inhibits angiogenesis and growth of HUVECs by regulating the Akt, JNK and NF-κB signaling pathways

Authors:
- Ke Ma
- Chuying Wang
- Qianqian Geng
- Yangwei Fan
- Jing Ning
- Haixia Yang
- Xuyuan Dong
- Danfeng Dong
- Yuyan Guo
- Xin Wei
- Enxiao Li
- Yinying Wu
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Affiliations: Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Medical Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Medical Oncology, Shaanxi Province People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: March 28, 2016 https://doi.org/10.3892/or.2016.4711
Pages: 3505-3513

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Abstract

Anginex is an artificial synthetic small molecule β-sheet-forming peptide shown to have anti-angiogenesis and antitumor effects in various solid tumors. However, its molecular mechanism remains largely unclear and efficient delivery methods for anginex remains to be developed. We report on the development of recombinant adeno-associated virus (rAAV2)-delivered anginex and the underlying mechanism of anti-angiogenesis and antitumor effects of anginex. We have successfully developed the rAAV2 vector to efficiently express anginex (rAAV2‑anginex). Transduction of rAAV2-anginex significantly induced apoptosis, and inhibited the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells in vitro. Western blot analysis revealed that rAAV2‑anginex inhibited the phosphorylation of Akt, while inducing the phosphorylation of JNK and activation of the NF-κB signaling pathway. In an in vivo CAM assay and xenograft model of SKOV3, rAAV2-anginex significantly reduced microvessel density (MVD) and vascular endothelial growth factor 165 (VEGF165), as demonstrated by immunohistochemistry analysis. Importantly, rAAV2-anginex inhibited tumor growth in an ovarian cancer SKOV3 cell nude mouse xenograft model. Our results suggest that rAAV2-anginex may inhibit tumor angiogenesis and growth through regulating Akt, JNK and NF-κB signaling pathways.

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