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

页码：31593 / 31603

页数：11

共 33 条

[31] The Interleukin-8 Pathway in Cancer
Waugh, David J. J.
Wilson, Catherine
[J]. CLINICAL CANCER RESEARCH, 2008, 14 (21) : 6735 - 6741
[32] Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells
Wilson, Catherine
Wilson, Timothy
Johnston, Patrick G.
Longley, Daniel B.
Waugh, David J. J.
[J]. MOLECULAR CANCER THERAPEUTICS, 2008, 7 (09) : 2649 - 2661
[33] Interleukin-8 and human cancer biology
Xie, KP
[J]. CYTOKINE & GROWTH FACTOR REVIEWS, 2001, 12 (04) : 375 - 391

← 1 2 3 4 →