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Salinomycin Inhibits Akt/NF-kB and Induces Apoptosis in Cisplatin Resistant Ovarian Cancer Cells
신소진,권상훈,차순도,비두르파라줄리,조치흠 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.98 No.-
The present study examined the effect of salinomycin to overcome cisplatin resistance in ovarian cancer. The cisplatin resistant ovarian cancer cells were cultured and treated with salinomycin. MTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation assay analyzed the effect on cell cycle and apoptosis. The expression of cell cycle regulatory-related proteins were evaluated by western blot analysis. The cell viability was significantly reduced by salinomycin treatment in a dose dependent manner. DNA fragmentation assay revealed apoptosis induction. Flow cytometry result showed that salinomycin increased the sub-G1 phase. Down regulation of Cdk2, Cdk4, up regulation of p27kip1 and concomitant increase in dephosphorylation of Rb were observed. Expression of survival protein Bcl-2 declined. Moreover, activation of caspase-3 and increased PARP cleavage triggered apoptosis. In order to evaluate the role of salinomycin in Akt/NF-kB pathway, the Akt, pAkt, I-kB and NF-κB levels were measured. Downregulated expression of Akt, pAkt, NF-κB and upregulation of I-κBα confirmed the Akt/NF-κB activation in this experiment. this study highlights the role of salinomycin in cisplatin resistant ovarian cancer, in particular Akt/NF-κB involved pathway that may provide a new approach to the clinical management of ovarian cancer.