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

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.

MeSH terms

  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics
  • DNA Repair
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics
  • Drug Resistance
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Female
  • Humans
  • I-kappa B Kinase* / genetics
  • I-kappa B Kinase* / metabolism
  • NF-kappa B* / genetics
  • NF-kappa B* / metabolism
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • RNA, Messenger / genetics

Substances

  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Endonucleases
  • ERCC1 protein, human
  • I-kappa B Kinase
  • NF-kappa B
  • RNA, Messenger