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苹果果胶:一种在体外对4T1乳腺癌细胞具有癌症抑制作用且在体内4T1癌瘤小鼠中表达p53的天然来源。

Apple pectin: A natural source for cancer suppression in 4T1 breast cancer cells in vitro and express p53 in mouse bearing 4T1 cancer tumors, in vivo.

作者信息

Delphi Ladan, Sepehri Houri

机构信息

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

出版信息

Biomed Pharmacother. 2016 Dec;84:637-644. doi: 10.1016/j.biopha.2016.09.080. Epub 2016 Sep 30.

Abstract

PURPOSE

Increase in the number of cancer related deaths has made the study on developing new drugs and treatments essential. One of the main aims in developing new therapies is to use natural resources which have the ability to induce apoptosis. Pectin is one of these natural compounds, a complex polysaccharide found in apples with anti-cancer properties. The aim of this study was to examine anti-cancer properties of pectic acid both in vitro in 4T1 breast cancer cells and in vivo using an animal model of breast cancer.

EXPERIMENTAL DESIGN

MTT cell proliferation assays, double fluorescence staining (acridine orange/ethidium bromide) and cell cycle analysis were employed to measure apoptosis in vitro. 4T1 cells were implanted into female BALB/c mice for in vivo studies. Then tumor volumes, histological analysis and immunohistochemical staining of P53 and tunnel test were applied to evaluate apoptosis in tumors.

RESULTS

The results of in vitro studies showed that concentration of 0.1% of pectic acid could induce apoptosis, inhibit cell growth (p<0.001) and reduce cell attachment, fragmented chromatin, and membrane blebbing as well as blocking the sub-G1 phase (p<0.001). In addition, in vivo studies showed that pectic acid could inhibit the progression of tumors through over-expression of P53 and increasing the number of apoptotic cells.

CONCLUSION

Our results demonstrated that pectic acid, a natural component of apple, can prevent metastasis in both cancer cell lines and primary tumors. This potential effect is mainly due to its ability to induce apoptosis.

摘要

目的

癌症相关死亡人数的增加使得研发新药和新疗法的研究变得至关重要。开发新疗法的主要目标之一是利用具有诱导细胞凋亡能力的自然资源。果胶就是这些天然化合物之一,它是一种存在于苹果中的具有抗癌特性的复合多糖。本研究的目的是在体外4T1乳腺癌细胞以及使用乳腺癌动物模型在体内研究果胶酸的抗癌特性。

实验设计

采用MTT细胞增殖测定、双重荧光染色(吖啶橙/溴化乙锭)和细胞周期分析来体外测量细胞凋亡。将4T1细胞植入雌性BALB/c小鼠体内进行体内研究。然后应用肿瘤体积、组织学分析以及P53的免疫组织化学染色和隧道试验来评估肿瘤中的细胞凋亡。

结果

体外研究结果表明,0.1%浓度的果胶酸可诱导细胞凋亡、抑制细胞生长(p<0.001)并减少细胞附着、染色质碎片化、细胞膜起泡以及阻断亚G1期(p<0.001)。此外,体内研究表明,果胶酸可通过P53的过表达和增加凋亡细胞数量来抑制肿瘤进展。

结论

我们的结果表明,苹果的天然成分果胶酸可在癌细胞系和原发性肿瘤中预防转移。这种潜在作用主要归因于其诱导细胞凋亡的能力。

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