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

被引：40
作者：
Stronach, Euan A. [1 ]
Cunnea, Paula [1 ]
Turner, Christina [2 ]
Guney, Tankut [2 ]
Aiyappa, Radhika [3 ]
Jeyapalan, Senthuran [2 ]
de Sousa, Camila H. [1 ]
Browne, Alacoque [2 ]
Magdy, Nesreen [2 ,4 ]
Studd, James B. [1 ]
Sriraksa, Ruethairat [5 ]
Gabra, Hani [1 ]
El-Bahrawy, Mona [2 ,6 ]
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London, England
[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Histopathol, London, England
[3] St Johns Res Inst, Div Mol Med, Bangalore, Karnataka, India
[4] Cairo Univ, Natl Canc Inst, Dept Pathol, Cairo, Egypt
[5] Int Agcy Res Canc, Epigenet Grp, F-69372 Lyon, France
[6] Univ Alexandria, Dept Pathol, Fac Med, Alexandria, Egypt
来源：
ONCOTARGET | 2015年 / 6卷 / 31期
关键词：
ovary; carcinoma; cytokine; interleukin-8; chemoresistance; CANCER CELLS; PACLITAXEL RESISTANCE; PROSTATE-CANCER; GROWTH-FACTOR; CHEMOTHERAPY; CISPLATIN; PROLIFERATION; ACTIVATION; EXPRESSION; APOPTOSIS;
D O I：
10.18632/oncotarget.3415
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：31593 / 31603
页数：11
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