<p>Lentivirus-Mediated VEGF Knockdown Suppresses Gastric Cancer Cell Proliferation and Tumor Growth in vitro and in vivo</p>

Abstract

Purpose: 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 lentivirusmediated 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.

Dual pH-Responsive and Tumor-Targeted Nanoparticle-Mediated Anti-Angiogenesis siRNA Delivery for Tumor Treatment

“…Some researchers have demonstrated that VEGF knockdown suppresses tumor cells proliferation. 27 To assess the cytotoxicity of the CHCE/siRNA NPs, the proliferation of SK-MEL-28 cells treated was tested by MTS. The results showed that the CHCE/siRNA NPs had the best anti-proliferation effect on the SK-MEL-28 cells ( Figure 5C ).…”

A Network Pharmacology Approach for Uncovering the Antitumor Effects and Potential Mechanisms of the Sijunzi Decoction for the Treatment of Gastric Cancer

“…The PPI network and KEGG results indicated that VEGFA was the main target in the treatment with SZJD against GC. VEGF is a well-known angiogenic factor and plays an important role in the proliferation, migration, and invasion of vascular endothelial cells [ 28 ]. The angiogenic pathway is a sound target for obstructing the excessive proliferation of cells because nutrients and growth factors are supplied through blood vessels to tumor cells [ 29 ].…”

Delivery of cancer therapies by synthetic and bio-inspired nanovectors

“…Transgenic viruses are also relatively simple to generate and they ensure a high level of transgene expression. Many studies were conducted with retrovirus-like particles (RLPs) [209], non-replicative adenoviruses [210] and AAVs [211], whereas other VLPs used for both their capacity to package DNA and their easy retargeting achieved lower transduction efficacy [68,82,212]. Despite several limitationsthe main one being the cytoplasmic delivery of cargos initially addressed to the nucleusnanoparticles (mainly lipid-based) have been extensively used for nucleic acid delivery [213][214][215].…”