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间充质干细胞治疗后小鼠乳腺肿瘤中微血管密度与c-Myc表达的相关性

Correlation of micro vessel density and c-Myc expression in breast tumor of mice following mesenchymal stem cell therapy.

作者信息

Adelipour Maryam, Babaei Fatemeh, Mirzababaei Mohammadreza, Allameh Abdolamir

机构信息

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Tissue Cell. 2017 Apr;49(2 Pt B):315-322. doi: 10.1016/j.tice.2017.01.007. Epub 2017 Jan 30.

DOI:10.1016/j.tice.2017.01.007
PMID:28209368
Abstract

Stem cell therapy for degenerative diseases has been established; however there are controversies over the treatment of solid tumors with stem cell transplantation. In the present study, the anti-tumor action of mesenchymal stem cells (MSCs) has been examined in a mouse model of breast cancer with emphasize on tumor growth, angiogenesis and c-Myc expression in breast tumors. For this purpose, MSCs were isolated from bone marrow of Balb/c mice and characterized. A Balb/c mouse model of breast cancer was developed and subjected to cell therapy intra venous (I.V) or intra tumor (I.T) with MSCs. Tumor growth was measured using a digital caliber for until the end of experiment (30days). Then the mice were sacrificed and their tumors were removed and processed for histopathological examination, immunohistochemical assay of CD31 and measuring of c-Myc expression using quantitative PCR. Detection of the labeled-MSCs in tumors following injection of the cells (I.V or I.T) clearly showed the homing of MSCs into tumors. Tumor growth in case of MSC-treated mice by I.V and I.T routes was inhibited by approximately 28% and 34% respectively compared to controls. The suppression of angiogenesis was reflected in Micro Vessel Density (MVD) following I.V or I.T delivery of the MSCs. c-Myc gene expression in tumor tissues of mice treated I.V or IT with MSCs was down-regulated to 28.0% and 16.0% respectively compare to control groups. In conclusion, growth inhibition of breast tumors in mice due to MSC therapy is associated with modulation of c-Myc activation and angiogenesis markers.

摘要

干细胞疗法已被用于治疗退行性疾病;然而,干细胞移植治疗实体瘤仍存在争议。在本研究中,我们在乳腺癌小鼠模型中研究了间充质干细胞(MSC)的抗肿瘤作用,重点关注肿瘤生长、血管生成以及乳腺癌组织中c-Myc的表达。为此,我们从Balb/c小鼠的骨髓中分离并鉴定了MSC。建立了Balb/c小鼠乳腺癌模型,并通过静脉注射(I.V)或瘤内注射(I.T)MSC进行细胞治疗。使用数字卡尺测量肿瘤生长,直至实验结束(30天)。然后处死小鼠,取出肿瘤并进行组织病理学检查、CD31免疫组化分析以及使用定量PCR测量c-Myc的表达。在静脉注射或瘤内注射细胞后,对肿瘤中标记的MSC进行检测,结果清楚地显示了MSC归巢至肿瘤。与对照组相比,静脉注射和瘤内注射MSC治疗的小鼠肿瘤生长分别受到约28%和34%的抑制。MSC静脉注射或瘤内注射后,微血管密度(MVD)反映了血管生成的抑制。与对照组相比,静脉注射或瘤内注射MSC治疗的小鼠肿瘤组织中c-Myc基因表达分别下调至28.0%和16.0%。总之,MSC治疗导致小鼠乳腺肿瘤生长抑制与c-Myc激活和血管生成标志物的调节有关。

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