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树枝状姜黄素纳米制剂对P53突变型和野生型癌细胞系的抗增殖和凋亡作用

Antiproliferative and Apoptotic Effect of Dendrosomal Curcumin Nanoformulation in P53 Mutant and Wide-Type Cancer Cell Lines.

作者信息

Montazeri Maryam, Pilehvar-Soltanahmadi Younes, Mohaghegh Mina, Panahi Alireza, Khodi Samaneh, Zarghami Nosratollah, Sadeghizadeh Majid

机构信息

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

Department of Molecular Biology and Biotechnology, University of Aix-Marseille, Marseille. France.

出版信息

Anticancer Agents Med Chem. 2017;17(5):662-673. doi: 10.2174/1871520616666160815124537.

Abstract

OBJECTIVE

The aim of this paper is to investigate the effect of dendrosomal curcumin (DNC) on the expression of p53 in both p53 mutant cell lines SKBR3/SW480 and p53 wild-type MCF7/HCT116 in both RNA and protein levels.

BACKGROUND

Curcumin, derived from Curcumin longa, is recently considered in cancer related researches for its cell growth inhibition properties. p53 is a common tumor-suppressor gene involved in cancers and its mutation not only inhibits tumor suppressor activity but also promotes oncogenic activity.

METHOD

Here, p53 mutant/Wild-type cells were employed to study the toxicity of DNC using MTT assay, Flow cytometry and Annexin-V, Real-time PCR and Western blot were used to analyze p53, BAX, Bcl-2, p21 and Noxa changes after treatment.

RESULTS

During the time, DNC increased the SubG1 cells and decreased G1, S and G2/M cells, early apoptosis also indicated the inhibition of cell growth in early phase. Real-Time PCR assay showed an increased mRNA of BAX, Noxa and p21 during the time with decreased Bcl-2. The expression of p53 mutant decreased in SKBR3/SW480, and the expression of p53 wild-type increased in MCF7/HCT116.

CONCLUSION

Consequently, p53 plays an important role in mediating the survival by DNC, which can prevent tumor cell growth by modulating the expression of genes involved in apoptosis and proliferation.

摘要

目的

本文旨在研究树状大分子姜黄素(DNC)对p53突变细胞系SKBR3/SW480和p53野生型细胞系MCF7/HCT116中p53在RNA和蛋白质水平表达的影响。

背景

姜黄素来源于姜黄,因其具有细胞生长抑制特性,最近在癌症相关研究中受到关注。p53是一种常见的参与癌症的肿瘤抑制基因,其突变不仅会抑制肿瘤抑制活性,还会促进致癌活性。

方法

在此,采用p53突变型/野生型细胞,通过MTT法研究DNC的毒性,使用流式细胞术和膜联蛋白-V,采用实时荧光定量PCR和蛋白质免疫印迹法分析处理后p53、BAX、Bcl-2、p21和Noxa的变化。

结果

在此期间,DNC增加了亚G1期细胞,减少了G1、S和G2/M期细胞,早期凋亡也表明早期细胞生长受到抑制。实时荧光定量PCR分析显示,在此期间BAX、Noxa和p21的mRNA增加,而Bcl-2减少。SKBR3/SW480中p53突变体的表达降低,而MCF7/HCT116中p53野生型的表达增加。

结论

因此,p53在介导DNC诱导的细胞存活中起重要作用,DNC可通过调节参与凋亡和增殖的基因表达来阻止肿瘤细胞生长。

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