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载白杨素的聚乳酸-羟基乙酸共聚物-聚乙二醇对小鼠4T1肿瘤模型中金属蛋白酶基因表达的影响。

The Effect of Chrysin Loaded PLGA-PEG on Metalloproteinase Gene Expression in Mouse 4T1 Tumor Model.

作者信息

Mohammadi Zoheyr, Sharif Zak Mohsen, Seidi Khaled, Barati Meisam, Akbarzadeh Abolfazl, Zarghami Nosratollah

机构信息

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Departments of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Drug Res (Stuttg). 2017 Apr;67(4):211-216. doi: 10.1055/s-0042-122136. Epub 2017 Feb 6.

DOI:10.1055/s-0042-122136
PMID:28166590
Abstract

Despite the advances in medicine, cancer remains as one of the leading causes of the death worldwide. Through our previous study, the Chrysin loaded PGLA/PEG has been synthesized, and its physico-chemical properties were characterized. The aim of the present study was to evaluate the Chrysin loaded PGLA/PEG nanoparticle therapeutic effects on TIMP-1, TIMP-2, MMP-2, MMP-9 and PI3k expression in Mouse 4T1 breast tumor model.30 mice were enrolled in the current study, and the mice were randomly divided into 3 groups: untreated (n=10), Chrysin treatment (n=10) and Chrysin-loaded PLGA/PEG-based treatment (n=10). 104T1 mammary carcinoma cells subcutaneously inoculated in the flank on mice orthotopically. After the treatments, the primary tumors were isolated from the Mice under anesthesia. For RNA extraction, the isolated tissues were frozen in -70°C. RNA extraction was performed by using RNA extraction kit. The expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 were measured by the real time PCR.The study results showed the expression of TIMP-1 and TIMP-2 in Chrysin-loaded PLGA/PEG treatment groups was higher than Chrysin receiving one. Also, the results showed that the MMP-9 and MMP-2 expressions were reduced after Chrysin loaded PLGA/PEG treatment. The reduction of the mentioned genes was greater in Chrysin-loaded PLGA/PEG treatment group in comparison with Chrysin receiving group.According to our present study, expression of the mentioned genes after treatments, Chrysin; especially, Chrysin-loaded PLGA/PEG could be proposed as a new component in the cancer therapy for reducing the progression and metastasis.

摘要

尽管医学取得了进步,但癌症仍然是全球主要的死亡原因之一。通过我们之前的研究,已合成了负载白杨素的PGLA/PEG,并对其物理化学性质进行了表征。本研究的目的是评估负载白杨素的PGLA/PEG纳米颗粒对小鼠4T1乳腺肿瘤模型中TIMP-1、TIMP-2、MMP-2、MMP-9和PI3k表达的治疗效果。本研究纳入了30只小鼠,将其随机分为3组:未治疗组(n = 10)、白杨素治疗组(n = 10)和负载白杨素的PLGA/PEG治疗组(n = 10)。将10个4T1乳腺癌细胞原位接种于小鼠侧腹皮下。治疗后,在麻醉下从小鼠体内分离出原发性肿瘤。为了提取RNA,将分离的组织在-70°C下冷冻。使用RNA提取试剂盒进行RNA提取。通过实时PCR测量TIMP-1、TIMP-2、MMP-2和MMP-9的表达。研究结果表明,负载白杨素的PLGA/PEG治疗组中TIMP-1和TIMP-2的表达高于接受白杨素治疗的组。此外,结果表明,负载白杨素的PLGA/PEG治疗后MMP-9和MMP-2的表达降低。与接受白杨素治疗的组相比,负载白杨素的PLGA/PEG治疗组中上述基因的降低幅度更大。根据我们目前的研究,治疗后上述基因的表达,尤其是负载白杨素的PLGA/PEG,可被提议作为癌症治疗中减少进展和转移的新成分。

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