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
  • View Affiliations

  • 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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April 2013
Volume 29 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang B, Wang X, Cai F, Chen W, Loesch U and Zhong XY: Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncol Rep 29: 1371-1378, 2013
APA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., & Zhong, X.Y. (2013). Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncology Reports, 29, 1371-1378. https://doi.org/10.3892/or.2013.2241
MLA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29.4 (2013): 1371-1378.
Chicago
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29, no. 4 (2013): 1371-1378. https://doi.org/10.3892/or.2013.2241