沙利霉素抑制Akt/NF-κB并诱导对顺铂耐药的卵巢癌细胞的凋亡

Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells

Objective: Salinomycin is a monocarboxylic polyether antibiotic which is extensively used as coccidiostat in poultry and commonly fed to ruminant animals to improve feed efficiency. Recently, It has been shown to be highly effective in elimination of cancer stem cells both in vitro and vivo but molecular mechanism for its anticancer effect is not clear. The present study examined the effect of salinomycin to overcome cisplatin resistance in ovarian cancer. Inhibition of Akt/NF-?B is the first report in salinomycin-mediated apoptosis of cisplatin resistant ovarian cancer cells (A2780cp).
Methods: The cancer cells were cultured and treated with salinomycin. MTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation were performed to determine the effect on cell cycle and apoptosis. The expression of cell cycle regulatory-related proteins were evaluated by western blot analysis.
Results: 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 induced sub-G1 arrest. Down regulation of Cdk2, Cdk4, up regulation of p27^kip1 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. Salinomycin treatment reduced the Akt, pAkt and NF-?B levels. Up regulation of I-?Ba further confirmed the NF-?B activation in this experiment.
Conclusion: Considering the importance of Akt/NF-?B signaling in cancer biology, the role of salinomycin may contribute to its toxicity towards cisplatin resistant ovarian cancer cells.

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