Gene therapy of renal cancer using recombinant adeno‑associated virus encoding human endostatin

Sun,Erlin; Han,Ruifa; Lu,Bingxin

doi:10.3892/ol.2018.9036

Gene therapy of renal cancer using recombinant adeno‑associated virus encoding human endostatin

Authors:
- Erlin Sun
- Ruifa Han
- Bingxin Lu
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Affiliations: Tianjin Key Laboratory of Urology Basic Science, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China, Department of Urology, Tianjin Nankai Hospital (Tianjin Hospital of Integrated Traditional Chinese and Western Medicine), Tianjin 300100, P.R. China
Published online on: June 28, 2018 https://doi.org/10.3892/ol.2018.9036
Pages: 2789-2796
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal cell carcinoma (RCC) is characterized by robust angiogenesis during tumor development. Various therapies are not able completely eradicated tumor relapse. The present study targeted angiogenesis and developed a recombinant adeno‑associated virus (rAAV) vector containing human endostatin gene for human kidney cancer gene therapy. Prophylactic and therapeutic RCC models were established in nude mice by subcutaneous inoculation of RCC cells and intra‑muscular or intra‑tumor injection of rAAV‑Endostatin. The growth of xenograft tumors was evaluated by tumor volume and weight. The microvessel density (MVD) was used to measure the anti‑angiogenesis effect of rAAV‑Endostatin. The toxic effect of rAAV‑Endostatin was also examined. In the therapeutic model, tumor‑bearing mice with rAAV‑Endostatin intra‑tumor injection demonstrated slow tumor growth (32.63±9.75) compared with control groups with intratumoral rAAV‑enhanced yellow florescent protein (EYFP) injections (21.50±11.42) and the RPMI‑1640 group (21.75±10.48 days, for tumors to reach ~300 mm3). MVD of the xenografts treated with rAAV‑Endostatin was 8.30±3.14/0.739 mm2 whereas that of control groups was 13.87±4.09/0.739 mm2 (rAVV‑EYFP) and 13.76±3.50/0.739 mm2 (RPMI‑1640). No significant side effects associated with rAAV‑endostatin use were identified in the vital organs. rAAV‑Endostatin demonstrated significant anti‑angiogenesis and antitumor activities. It may serve as an effective agent for renal cancer gene therapy.

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