Newcastle disease virus expressing an angiogenic inhibitor exerts an enhanced therapeutic efficacy in colon cancer model

Abstract

Newcastle disease virus (NDV)-mediated gene therapy is a promising new approach for treatment of cancer but shows limited anti-angiogenesis. VEGF-Trap plays a vital role in anti-angiogenesis. To enhance the anti-tumor effect of NDV, VEGF-Trap gene was incorporated into the genome of rNDV in this study (named rNDV-VEGF-Trap). Results showed that rNDV-VEGF-Trap reduced cell growth ratio by 85.37% and migration ratio by 87.9% in EA.hy926 cells. In vivo studies, rNDV-VEGF-Trap reduced tumor volume and weight of CT26-bearing mice by more than 3 folds. Immunohistochemistry analysis of CD34 showed rNDV-VEGF-Trap significantly decreased the number of vascular endothelial cells in the tumor tissues. Moreover, Western blot analysis demonstrated that treatment with rNDV-VEGF-Trap significantly decreased the phosphorylation levels of AKT, ERK1/2 and STAT3 and increased the expression levels of P53, BAX and cleaved caspase-3 in the tumor tissue. In addition, to evaluate the toxicity of rNDV-VEGF-Trap, serum chemistries were analyzed. The results showed that rNDV-VEGF-Trap caused insignificant changes of creatinine levels, alanine aminotransferase and aspartate transaminase. Furthermore, administration of rNDV-VEGF-Trap did not cause the diarrhoea, decreased appetite, weight decrease and haemorrhage of the experimental mice. These data suggest that rNDV-VEGF-Trap exhibits an enhanced inhibition of CT26-bearing mice by enhancing anti-angiogenesis and apoptosis and may be a potential candidate for carcinoma therapy especially for colon cancer.

Effect of Mammary Adenocarcinoma Supernatant on Hepatic Fibroblast Differentiation

“…In 2006, Jian-Guo CAO et al proposed the concept of a "premetastatic niche" (PMN), that is, tumor cells in the primary lesions remotely destroy the molecular niche of premetastatic lesions before cancer cell metastasis [6]. At this time, cytokines such as CCL5, IL-17B, FAK, p-P38, and TGF in the PMN become significantly unbalanced and deteriorate, which induces inflammatory reactions and forms immune cell traps [7]. Meanwhile, cancer-associated fibroblasts (CAFs) are recruited to premetastatic lesions, where they become premetastatic-associated fibroblasts and cause further PMN deterioration [8].…”

Side population cells derived from hUCMSCs and hPMSCs could inhibit the malignant behaviors of Tn+ colorectal cancer cells from modifying their O-glycosylation status

“…Due to changes of life style and diet-related factors, morbidity is on the rise in recent years [ 2 ]. Traditional therapeutic methods such as surgical treatment, radiotherapy, and chemotherapy have the disadvantages of high recurrence rate and adverse reactions[ 3 ]. Furthermore, on account of the absence of early symptoms, many patients are diagnosed in the middle or advanced stages and often present local invasion and distant metastasis, which leads to a poor prognosis [ 4 , 5 ].…”