Lentivirus-Mediated VEGF Knockdown Suppresses Gastric Cancer Cell Proliferation and Tumor Growth in vitro and in vivo
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Jong-Hyung Park,1,2 Jin-Hee Seo,3 Hee-Yeon Jeon,1,4 Sun-Min Seo,1 Han-Kyul Lee,1 Jin-Il Park,1,2 Jun-Young Kim,1 Yang-Kyu Choi1 1Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea; 2Helixmith Co. Ltd., Seoul 08826, Republic of Korea; 3Laboratory Animal Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea; 4Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of KoreaCorrespondence: Yang-Kyu ChoiDepartment of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of KoreaTel +82-2-2049-6113Fax +82-2-450-3037Email yangkyuc@konkuk.ac.krPurpose: Gastric cancer has a high mortality rate worldwide. Although treatments, such as molecular-targeted therapy, have been introduced, the resulting long-term survival and prognosis remain unsatisfactory. Downregulation of the target genes using lentivirus-mediated short hairpin RNA (shRNA) can be an effective therapeutic strategy for patients with gastric cancer. Overexpressed vascular endothelial growth factor A (VEGF) in human gastric cancer cells can be an effective novel therapeutic target for human gastric cancer. Thus, this study aimed to evaluate the therapeutic effects of lentivirus-mediated knockdown of VEGF gene expression in human gastric cancer growth.Materials and Methods: Specific shRNA sequences targeting VEGF were designed to construct a lentiviral expression vector. After human gastric carcinoma cells (cell line NCI-N87) were infected with the lentiviral vector, the therapeutic effects of the lentivirus-mediated shRNA targeting VEGF were analyzed both in vitro and in vivo.Results: Stable suppression of VEGF gene expression in NCI-N87 cells using shRNA (ShVEGF) showed significant inhibition of cell proliferation, clonogenicity, and cell motility. ShVEGF also showed increased G0/G1 cell cycle arrest and apoptosis. In addition, in vivo results from nude mice xenografted ShVEGF showed significant inhibition of tumor growth. Assessing the therapeutic effects of intratumoral injection of lentivirus-targeting VEGF (Virus_VEGF) revealed that it significantly inhibited tumor growth compared to that in the Virus_Scramble or saline injection control groups.Conclusion: The constructed ShVEGF showed significant inhibition of NCI-N87 gastric cancer cell growth both in vitro and in vivo. These experimental results suggest a novel therapeutic strategy for patients with gastric cancer using lentivirus-mediated shRNA targeting VEGF.Keywords: gastric carcinoma, NCI-N87, ShRNA, VEGF
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