OBJECTIVE: Cancer stem cells (CSCs) represent a subpopulation of undifferentiated tumorigenic cells responsible for tumor initiation, maintenance, drug resistance and metastasis of tumors. CSCs involved in drug resistance and relapse of cancers can significantly affect ovarian cancer therapy. The antibiotics salinomycin has recently been shown to be a potent compound to deplete chemoresistant cells in adenocarcinoma. The objective of the present study was to evaluate the effect of salinomycin on ovarian CSC whereby salinomycin mono-and combination treatment with paclitaxol regimend were analyzed.
METHODS: The CD44+CD117+CSCs were isolated from the primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer by using immune magnetic-activated cell sorting system. To evaluate the effect of salinomycin on ovarian CSC, cells were treated in single and combined treatment. The expression was Nanog, Oct3/4, Sox2 and ABCG2 mRNA was determined by RT-PCR and protein expression was detected by Western blot analysis. The cell viability assay, gelatin zymography and apoptosis assay were applied to evaluate the effects of salinomycin compared with parental tumor cells and CSCs.
RESULTS: The combination of salinomycin with paclitaxel (PTX) was enhanced change cell viability or activating apoptosis in CD44+CD117+ cells, whereas the salinomycin monotreatment did not cause significant changes. Salinomycin treatment reduced stemness gene expression and suppressed invasion of CSCs.
CONCLUSIONS: Based on our findings, we concluded that anti-cancer effect of salinomycin with PTX reduced stemness and induced apoptosis in ovarian cancer and cancer stem cells.
Citation Format: So-Jin Shin, Jin-Young Kim, Hyun-Gyo Lee, Eun-Ji Nam, Chi-Heum Cho. Salinomycin have antiproliferative and apoptotic effects on ovarian cancer stem-like cell. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 217. doi:10.1158/1538-7445.AM2014-217