The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma
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Euan A. Stronach1, Paula Cunnea1, Christina Turner2, Tankut Guney2, Radhika Aiyappa3, Senthuran Jeyapalan2, Camila H. de Sousa1, Alacoque Browne2, Nesreen Magdy2,4, James B. Studd1, Ruethairat Sriraksa5, Hani Gabra1, Mona El-Bahrawy2,6
1Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK
2Department of Histopathology, Imperial College London, Hammersmith Hospital, London, UK
3Division of Molecular Medicine, St. John's Research Institute, Bangalore, India
4Department of Pathology, National Cancer Institute, Cairo University, Egypt
5Epigenetics Group, International Agency for Research on Cancer, Lyon, France
6Department of Pathology, Faculty of Medicine, University of Alexandria, Egypt
Mona El-Bahrawy, e-mail: firstname.lastname@example.org
Keywords: ovary, carcinoma, cytokine, interleukin-8, chemoresistance
Received: November 30, 2014 Accepted: February 19, 2015 Published: March 23, 2015
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.
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