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2010•Immunological JournalRequires access

The mechanism of exogenous IL-8-caused cisplatin and paclitaxel resistance of ovarian cancer cells and its related signal transduction pathways

Suqing Wang

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Abstract

In this study,we aimed to discover the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.Based on our previous studies,the effect of exogenous IL-8 on the sensitivity to cisplatin and paclitaxel in ovarian cancer cells was investigated.Meanwhile,we also investigated the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.A2780,which do not express IL-8 and sensitive to cisplatin and paclitaxel,and SKOV-3 cells,which constitutively express high levels of IL-8 and resistant to cisplatin and paclitaxel,are suitable models for this study.We found that pretreatment of A2780 cells with IL-8 caused 6.07-fold and 7.23-fold increase in resistance to cisplatin and paclitaxel,respectively,whereas SKOV-3 cells exhibited 8.22-fold and 9.03-fold increase,respectively. IL-8 enhanced the expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes(Bcl-2, Bcl-xL and XIAP) in A2780 and SKOV-3 cells.Pretreatment of A2780 cells with MEK1/2 or PI3K inhibitors blocked IL-8-induced cisplatin and paclitaxel resistance.These data suggest that IL-8 may confer cisplatin and paclitaxel resistance in ovarian cancer cells by increasing expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes Bcl-2,Bcl-xL and XIAP.These activity of IL-8 is dependent on Ras/Raf/MEK/MAPK and PI3K/Akt signal transduction pathways.

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What this paper is about

In this study,we aimed to discover the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.Based on our previous studies,the effect of exogenous IL-8 on the sensitivity to cisplatin and paclitaxel in ovarian cancer cells was investigated.Meanwhile,we also investigated the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.A2780,which do not express IL-8 and sensitive to cisplatin and paclitaxel,and SKOV-3 cells,which constitutively express high levels of IL-8 and resistant to cisplatin and paclitaxel,are suitable models for this study.We found that pretreatment of A2780 cells with IL-8 caused 6.07-fold and 7.23-fold increase in resistance to cisplatin and paclitaxel,respectively,whereas SKOV-3 cells exhibited 8.22-fold and 9.03-fold increase,respectively. IL-8 enhanced the expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes(Bcl-2, Bcl-xL and XIAP) in A2780 and SKOV-3 cells.Pretreatment of A2780 cells with MEK1/2 or PI3K inhibitors blocked IL-8-induced cisplatin and paclitaxel resistance.These data suggest that IL-8 may confer cisplatin and paclitaxel resistance in ovarian cancer cells by increasing expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes Bcl-2,Bcl-xL and XIAP.These activity of IL-8 is dependent on Ras/Raf/MEK/MAPK and PI3K/Akt signal transduction pathways.

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Available abstract

In this study,we aimed to discover the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.Based on our previous studies,the effect of exogenous IL-8 on the sensitivity to cisplatin and paclitaxel in ovarian cancer cells was investigated.Meanwhile,we also investigated the mechanism of cisplatin and paclitaxel resistance caused by exogenous IL-8 in ovarian cancer cells and its related signal pathways.A2780,which do not express IL-8 and sensitive to cisplatin and paclitaxel,and SKOV-3 cells,which constitutively express high levels of IL-8 and resistant to cisplatin and paclitaxel,are suitable models for this study.We found that pretreatment of A2780 cells with IL-8 caused 6.07-fold and 7.23-fold increase in resistance to cisplatin and paclitaxel,respectively,whereas SKOV-3 cells exhibited 8.22-fold and 9.03-fold increase,respectively. IL-8 enhanced the expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes(Bcl-2, Bcl-xL and XIAP) in A2780 and SKOV-3 cells.Pretreatment of A2780 cells with MEK1/2 or PI3K inhibitors blocked IL-8-induced cisplatin and paclitaxel resistance.These data suggest that IL-8 may confer cisplatin and paclitaxel resistance in ovarian cancer cells by increasing expression of drug resistance-associated gene MDR1 and apoptosis-inhibiting genes Bcl-2,Bcl-xL and XIAP.These activity of IL-8 is dependent on Ras/Raf/MEK/MAPK and PI3K/Akt signal transduction pathways.

Key concepts: Cisplatin, XIAP, Paclitaxel, Ovarian cancer, Apoptosis, Cancer research, Signal transduction, PI3K/AKT/mTOR pathway

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