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鼻咽癌中Slug介导的Puma/p53信号通路与放疗抵抗之间的临床关系。

The clinical relationship between the slug-mediated Puma/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma.

作者信息

Xu T, Yuan Y, Xiao D-J

机构信息

Department of Otolaryngology, The Second People's Hospital of Wuxi, Wuxi, Jiangsu, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Mar;21(5):953-958.

PMID:28338201
Abstract

OBJECTIVE

To explore the clinical relationship between the Slug-mediated Puma/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma.

PATIENTS AND METHODS

Forty surgical specimens were collected from nasopharyngeal carcinoma patients treated at our hospital between February 2010 and February 2015. Twenty patients with poorly differentiated nasopharyngeal carcinoma with and without radiotherapy resistance were included in the experimental and control groups, respectively. Slug, Puma, and p53 expression were quantified in all tissues using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.

RESULTS

Slug and p53 mRNA levels were significantly higher in the experimental group than in the control group (p < 0.01). Puma mRNA levels were significantly lower in the experimental group than in the control group (p < 0.01). Slug protein expression was significantly higher in the experimental group (6.07 ± 0.203 μg/L) than in the control group (1.24 ± 0.171 μg/L) (p < 0.01). p53 protein expression was significantly higher in the experimental group (4.28 ± 0.108 μg/L) than in the control group (0.63 ± 0.101 μg/L) (p < 0.01). Puma protein expression was significantly lower in the experimental group (0.43 ± 0.11 μg/L) than in the control group (3.37 ± 0.112 μg/L) (v < 0.01). The number of Slug, Puma, and p53-positive cells in the experimental group and the control group were quantified; these values confirmed the ELISA and Western blot findings.

CONCLUSIONS

Slug downregulated the Puma protein expression signaling pathway and promoted radiotherapy resistance in poorly differentiated squamous cell carcinoma tissue, in a p53-independent manner.

摘要

目的

探讨Slug介导的Puma/p53信号通路与鼻咽癌放疗抵抗之间的临床关系。

患者与方法

收集2010年2月至2015年2月在我院接受治疗的鼻咽癌患者的40份手术标本。实验组和对照组分别纳入20例低分化鼻咽癌患者,其中实验组患者具有放疗抵抗,对照组患者无放疗抵抗。采用荧光定量聚合酶链反应、酶联免疫吸附测定(ELISA)、蛋白质免疫印迹法和免疫组织化学法对所有组织中的Slug、Puma和p53表达进行定量分析。

结果

实验组中Slug和p53 mRNA水平显著高于对照组(p<0.01)。实验组中Puma mRNA水平显著低于对照组(p<0.01)。实验组中Slug蛋白表达(6.07±0.203μg/L)显著高于对照组(1.24±0.171μg/L)(p<0.01)。实验组中p53蛋白表达(4.28±0.108μg/L)显著高于对照组(0.63±0.101μg/L)(p<0.01)。实验组中Puma蛋白表达(0.43±0.11μg/L)显著低于对照组(3.37±0.112μg/L)(p<0.01)。对实验组和对照组中Slug、Puma和p53阳性细胞数量进行定量分析;这些结果证实了ELISA和蛋白质免疫印迹法的结果。

结论

在低分化鳞状细胞癌组织中,Slug以不依赖p53的方式下调Puma蛋白表达信号通路并促进放疗抵抗。

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