Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation

Zhang,Bei; Wang,Xueya; Cai,Fengfeng; Chen,Weijie; Loesch,Uli; Zhong,Xiao  Yan

doi:10.3892/or.2013.2241

Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation

Authors:
- Bei Zhang
- Xueya Wang
- Fengfeng Cai
- Weijie Chen
- Uli Loesch
- Xiao Yan Zhong
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Affiliations: Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland, Nanomedicine Research Group, Medical Intensive Care Unit, University Hospital Basel, CH-4031 Basel, Switzerland, Hospital Pharmacy, University Hospital Basel, CH-4031 Basel, Switzerland
Published online on: January 17, 2013 https://doi.org/10.3892/or.2013.2241
Pages: 1371-1378

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Abstract

In order to search for alternative agents to overcome chemoresistance during the treatment of ovarian cancer, this study aimed to examine the anticancer effects and action mechanism of salinomycin, a selective inhibitor of cancer stem cells, on cisplatin-resistant human ovarian cancer cell lines in vitro and in vivo. The concentration- (0.01-200 µM) and time‑dependent (24-72 h) growth inhibitory effects of salinomycin were observed in the ovarian cancer cell lines OV2008, C13, A2780, A2780-cp, SKOV3 and OVCAR3, by measuring cell viability using the resazurin reduction assay. The IC50 (24 h) range of salinomycin on the six cell lines was found to be 1.7-7.4 µM. After cisplatin-resistant C13 cells were treated with salinomycin, the percentage of apoptotic cells determined by flow cytometry was significantly increased, in a concentration- and time‑dependent manner. However, no cell cycle arrest was detected in the G1/G0, S and G2/M phases in the salinomycin‑treated and control cells. The Bio-Plex phosphoprotein 5-plex assay (Akt, IκB-α, ERK1/2, JNK and p38 MAPK) demonstrated a marked time- and concentration‑dependent increase in the phosphorylation of p38 MAPK, subsequent to salinomycin treatment. Moreover, salinomycin significantly suppressed tumor growth in a tumor xenograft model. These findings suggested that salinomycin efficiently inhibits the cisplatin-resistant human ovarian cancer cell line growth through the induction of apoptosis, potentially associated with the p38 MAPK activation.

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