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核因子-κB(NF-κB)和IκB激酶β(IKKβ)在上皮性卵巢癌中的表达水平及其与耐药相关基因多药耐药基因1(MDR1)、拓扑异构酶II(TOPOII)和切除修复交叉互补基因1(ERCC1)的相关性

The expression levels of NF-κB and IKKβ in epithelial ovarian cancer and their correlation with drug resistance-related genes MDR1, TOPOII, and ERCC1.

作者信息

Hu Zhexia, Cang Rong, Zhang Hui, Gao Yu, Zhang Xueling, Chen Xiao, Rong Yun, Luo Biyun, Gao Yingfang

机构信息

Department of Gynaecology and Obstetrics, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

Department of Gynecological Endocrinology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.

出版信息

Acta Biochim Pol. 2023 Feb 17;70(1):23-29. doi: 10.18388/abp.2020_5727.

Abstract

OBJECTIVES

To explore the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of nuclear factor kappa B kinase (IKKβ) in epithelial ovarian cancer and the correlation analysis with multi-drug resistance-related genes 1 (MDR1), topoisomerase II (TOPOII) and nucleotide excision repair cross complementary group 1 (ERCC1).

METHODS

Immunohistochemical methods were used to detect the expression levels of NF-κB and IKKβ in epithelial ovarian cancer group (50 cases), ovarian benign tumor group (30 cases), and normal ovary group (10 cases). The expression levels of NF-κB, IKKβ, MDR1, TOPOII and ERCC1 messenger ribonucleic acid (mRNA) and protein were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. Student's t-test and one-way ANOVA were used for comparison of numerical data. Pearson's chi-squared and Fisher's exact tests were carried out for analysis of non-numerical data.

RESULTS

The levels of NF-κB, IKKβ, MDR1 and ERCC1 mRNA and protein were increased (P<0.05), and the expression levels of TOPOII were decreased (P<0.05) in the epithelial ovarian cancer group compared to the normal ovary and benign ovarian tumor groups. The expression of NF-κB and IKKβ in epithelial ovarian cancer was significantly increased in patients with higher tumor stage, lower differentiation and presence of lymph node metastasis and positively correlated with MDR1 expression. NF-κB and IKKβ were negatively correlated with the expression of TOPOII and antagonized each other with TOPOII.

CONCLUSIONS

The expression of NF-κB and IKKβ was positively correlated with the expression of MDR1, and negatively correlated with the expression of TOPOII. The correlation of NF-κB, IKKβ and resistance related genes, including MDR1, TOPOII, ERCC1, can predict the resistance of chemotherapy individuals to chemotherapy.

摘要

目的

探讨核因子κB(NF-κB)及核因子κB激酶抑制剂(IKKβ)在上皮性卵巢癌中的表达水平,并分析其与多药耐药相关基因1(MDR1)、拓扑异构酶II(TOPOII)及核苷酸切除修复交叉互补基因1(ERCC1)的相关性。

方法

采用免疫组织化学方法检测上皮性卵巢癌组(50例)、卵巢良性肿瘤组(30例)及正常卵巢组(10例)中NF-κB和IKKβ的表达水平。运用实时定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法分析NF-κB、IKKβ、MDR1、TOPOII及ERCC1信使核糖核酸(mRNA)和蛋白质的表达水平。采用学生t检验和单因素方差分析比较数值数据。采用Pearson卡方检验和Fisher精确检验分析非数值数据。

结果

与正常卵巢组和卵巢良性肿瘤组相比,上皮性卵巢癌组中NF-κB、IKKβ、MDR1及ERCC1的mRNA和蛋白质水平升高(P<0.05),TOPOII的表达水平降低(P<0.05)。上皮性卵巢癌患者中,肿瘤分期较高、分化程度较低及存在淋巴结转移者的NF-κB和IKKβ表达显著升高,且与MDR1表达呈正相关。NF-κB和IKKβ与TOPOII的表达呈负相关,且与TOPOII相互拮抗。

结论

NF-κB和IKKβ的表达与MDR1的表达呈正相关,与TOPOII的表达呈负相关。NF-κB、IKKβ与包括MDR1、TOPOII、ERCC1在内的耐药相关基因的相关性可预测化疗个体对化疗的耐药性。

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