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氟-18氟脱氧葡萄糖在肝细胞癌中的摄取:与葡萄糖转运蛋白及p53表达的相关性

Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma: Correlation with Glucose Transporters and p53 Expression.

作者信息

Brito Ana F, Abrantes Ana M, Ribeiro Marina, Oliveira Rui, Casalta-Lopes João, Gonçalves Ana C, Sarmento-Ribeiro Ana B, Tralhão José G, Botelho Maria F

机构信息

Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal ; Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal ; CNC.IBILI, University of Coimbra, Coimbra, Portugal.

Biophysics Unit, Faculty of Medicine of University of Coimbra, Coimbra, Portugal ; Center of Investigation on Environmental, Genetics and Oncobiology (CIMAGO), Faculty of Medicine of University of Coimbra, Coimbra, Portugal.

出版信息

J Clin Exp Hepatol. 2015 Sep;5(3):183-9. doi: 10.1016/j.jceh.2015.05.003. Epub 2015 Jun 3.

Abstract

INTRODUCTION

Hepatocellular Carcinoma (HCC) is one of most lethal cancers worldwide. The prognosis is very poor and therapeutic options are limited. The aim of this study was to determine the correlation of the [(18)F]FDG uptake profile of three HCC cell lines with p53 and glucose transporters (GLUTs) 1, 2, 3, 5 and 12 expression and with the glucose level present in the cell culture medium.

METHODS

Cell lines used are HepG2 (wp53), HuH7 (overexpress p53) and Hep3B2.1-7 (p53null). An immunocytochemical analysis was performed to evaluate p53 expression. Through uptake studies were analyzed the [(18)F]FDG uptake profiles of all cell lines under study. The expression of GLUTs were quantified by flow cytometry. The [(18)F]FDG uptake studies GLUTs expression analysis were performed on cells that grew in a high and low glucose medium in order to determine the effect of glucose concentration on GLUTs expression and on [(18)F]FDG uptake.

RESULTS

Immunocytochemical analysis confirmed the p53 expression profiles of all cell lines. It was found out that for all cell lines, [(18)F]FDG uptake is higher when cells grow in low glucose medium, however, the glucose level doesn't affect mostly the GLUTs expression. The Hep3B2.1-7 (p53null) is always the one that have higher [(18)F]FDG uptake. It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines.

CONCLUSIONS

Our results shown that the p53 expression influences [(18)F]FDG uptake. This suggests that [(18)F]FDG may be used in HCC diagnosis, and may even provide some information about the genetic profile of the tumor.

摘要

引言

肝细胞癌(HCC)是全球最致命的癌症之一。其预后很差,治疗选择有限。本研究的目的是确定三种肝癌细胞系的[(18)F]FDG摄取情况与p53、葡萄糖转运蛋白(GLUTs)1、2、3、5和12的表达以及细胞培养基中葡萄糖水平之间的相关性。

方法

使用的细胞系为HepG2(野生型p53)、HuH7(p53过表达)和Hep3B2.1-7(p53缺失)。进行免疫细胞化学分析以评估p53表达。通过摄取研究分析了所有研究细胞系的[(18)F]FDG摄取情况。通过流式细胞术对GLUTs的表达进行定量。在高糖和低糖培养基中生长的细胞上进行[(18)F]FDG摄取研究和GLUTs表达分析,以确定葡萄糖浓度对GLUTs表达和[(18)F]FDG摄取的影响。

结果

免疫细胞化学分析证实了所有细胞系的p53表达情况。结果发现对于所有细胞系,当细胞在低糖培养基中生长时[(18)F]FDG摄取更高,然而,葡萄糖水平对GLUTs表达的影响不大。Hep3B2.1-7(p53缺失)总是[(18)F]FDG摄取较高的细胞系。还发现这些细胞系并不总是GLUT1和GLUT3表达最多。

结论

我们的结果表明p53表达会影响[(18)F]FDG摄取。这表明[(18)F]FDG可用于肝癌诊断,甚至可能提供有关肿瘤基因特征的一些信息。

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