The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma
Author(s)
Type
Journal Article
Abstract
Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.
Date Issued
2015-03-23
Date Acceptance
2015-02-19
Citation
Oncotarget, 2015, 6 (31), pp.31593-31603
ISSN
1949-2553
Publisher
Impact Journals
Start Page
31593
End Page
31603
Journal / Book Title
Oncotarget
Volume
6
Issue
31
Copyright Statement
© The Authors 2015. Licensed under a Creative Commons Attribution 3.0 License.
License URL
Sponsor
Royal College of Pathologists
Grant Number
WMEP_P24521
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
ovary
carcinoma
cytokine
interleukin-8
chemoresistance
CANCER CELLS
PACLITAXEL RESISTANCE
PROSTATE-CANCER
GROWTH-FACTOR
CHEMOTHERAPY
CISPLATIN
PROLIFERATION
ACTIVATION
EXPRESSION
APOPTOSIS
Publication Status
Published