The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma

Autor: Mona El-Bahrawy, Alacoque Browne, Radhika Aiyappa, Nesreen Magdy, Senthuran Jeyapalan, Camila H. de Sousa, Hani Gabra, Ruethairat Sriraksa, Euan A. Stronach, Tankut G. Guney, Christina Turner, Paula Cunnea, James B. Studd
Přispěvatelé: Royal College of Pathologists
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Time Factors
endocrine system diseases
medicine.medical_treatment
carcinoma
Receptors
Interleukin-8B
Receptors
Interleukin-8A
ACTIVATION
Antineoplastic Combined Chemotherapy Protocols
cytokine
Phosphorylation
Receptor
Ovarian Neoplasms
Gene knockdown
PROLIFERATION
chemoresistance
CHEMOTHERAPY
Receptor antagonist
PROSTATE-CANCER
APOPTOSIS
Cytokine
Oncology
Proto-Oncogene Proteins c-bcl-2
Female
RNA Interference
bcl-Associated Death Protein
Signal transduction
Life Sciences & Biomedicine
medicine.drug
Research Paper
Signal Transduction
EXPRESSION
medicine.medical_specialty
GROWTH-FACTOR
medicine.drug_class
Biology
Transfection
Internal medicine
Cell Line
Tumor
medicine
Humans
CANCER CELLS
Cisplatin
Science & Technology
Dose-Response Relationship
Drug
Interleukin-8
Cell Biology
medicine.disease
Endocrinology
Drug Resistance
Neoplasm
Cancer cell
Cancer research
ovary
PACLITAXEL RESISTANCE
Neoplasm Grading
Ovarian cancer
Neoplasms
Cystic
Mucinous
and Serous
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: 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.
Databáze: OpenAIRE
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