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溶瘤呼肠孤病毒感染后脂肪来源间充质干细胞的抗癌活性增强。

Anti-cancer Activity of Adipose-Derived Mesenchymal Stem Cells Increased after Infection with Oncolytic Reovirus.

作者信息

Babaei Abouzar, Bannazadeh Baghi Hossein, Nezhadi Akram, Jamalpoor Zahra

机构信息

Trauma Research Center, Aja University of Medical Sciences, Tehran, Iran.

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Adv Pharm Bull. 2021 Feb;11(2):361-370. doi: 10.34172/apb.2021.034. Epub 2020 Apr 20.

Abstract

Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the family, kills KRAS mutant cancer cells. However, the use of OVs has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anti-cancer effects of human adipose derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human glioblastoma cells. Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time polymerase chain reaction (PCR), and different in vitro anti-cancer experiments were applied for our anti-cancer purposes. Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D. AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line.

摘要

3型迪林呼肠孤病毒(ReoT3D)是该家族的一种野生型溶瘤病毒(OV),可杀死KRAS突变癌细胞。然而,溶瘤病毒的使用面临一些限制,如免疫反应以及在全身治疗中将溶瘤病毒递送至肿瘤部位。为了解决这一问题,并增强这些溶瘤病毒的抗癌效果,间充质干细胞(MSCs)可作为溶瘤病毒递送的有效载体。在本研究中,我们检测了人脂肪来源的间充质干细胞(AD-MSCs)作为ReoT3D载体对人胶质母细胞瘤细胞的抗癌作用。在此,对AD-MSCs进行了表征,并通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法测定了ReoT3D对它们的毒性。然后,通过实时聚合酶链反应(PCR)评估AD-MSCs产生病毒的能力,并应用不同的体外抗癌实验来实现我们的抗癌目的。我们的毒性试验结果表明,分离和培养的AD-MSCs对感染复数(MOI)>1 pfu/细胞的无毒浓度的ReoT3D具有抗性。此外,结果表明AD-MSCs易受病毒生命周期互补作用的影响,并且有能力产生子代病毒。此外,我们的结果表明AD-MSCs具有溶瘤作用,并增强了ReoT3D的抗癌效果。AD-MSCs作为溶瘤呼肠孤病毒的易感宿主,可以增强这种溶瘤病毒对多形性胶质母细胞瘤(GBM)细胞系的抗癌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1485/8046384/d76da8117c2f/apb-11-361-g001.jpg

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