Journal
CYTOKINE
Volume 56, Issue 2, Pages 365-375Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2011.06.005
Keywords
Interleukin-8 (IL-8); Chemoresistance; Mutidrug resistance-related genes; Apoptosis inhibitory proteins; Ovarian cancer (OVCA)
Funding
- National Natural Science Foundation of China [81041071]
- Tianjin Municipal Science and Technology Commission [08JCYBJC06900]
- Postdoctoral Science Foundation of China [20080441340]
- Medical College of Chinese People's Armed Police Forces [WYM201105, WY200914]
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It has been widely reported that interleukin-8 (IL-8) is overexpressed in ovarian cyst fluid, ascites, serum, and tumor tissue from ovarian cancer (OVCA) patients, and elevated IL-8 expression correlates with a poor final outcome and chemosensitivity. However, the role of IL-8 expression in the acquisition of the chemoresistance phenotype and the underlining mechanisms of drug resistance in OVCA cells are not yet fully understood. Here we show that both exogenous (a relatively short period of treatment with recombination IL-8) and endogenous IL-8 (by transfecting with plasmid encoding for sense IL-8) induce cisplatin and paclitaxel resistance in non-IL-8-expressing A2780 cells, while deleting of endogenous IL-8 expression in IL-8-overexpressing SKOV-3 cells (by transfecting with plasmid encoding for antisense IL-8) promotes the sensitivity of these cells to anticancer drugs. IL-8-mediated resistance of OVCA cells exhibits decreased proteolytic activation of caspase-3. Meanwhile, the further study demonstrates that the chemoresistance caused by IL-8 is associated with increased expression of both multidrug resistance-related genes (MDR1) and apoptosis inhibitory proteins (Bcl-2, Bcl-xL, and XIAP), as well as activation of PI3 K/Akt and Ras/MEK/ERK signaling. Therefore, modulation of IL-8 expression or its related signaling pathway may be a promising strategy of treatment for drug-resistant OVCA. (C) 2011 Published by Elsevier Ltd,
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