Flap endonuclease 1 (FEN1) overexpression promotes breast cancer. We investigated the role of FEN1 in cisplatin resistance and the chemosensitizing effects of curcumin in breast cancer cells. We demonstrated that FEN1 overexpression promotes cisplatin resistance in breast cancer cells, and that FEN1 knockdown enhances cisplatin sensitivity. Curcumin down-regulated FEN1 expression in a dose-dependent manner. A combination of cisplatin and curcumin enhanced breast cancer cell sensitivity to cisplatin by down-regulating FEN1 expression in vitro and in vivo. Increased ERK phosphorylation contributed to cisplatin resistance and cisplatin-induced FEN1 overexpression in breast cancer cells. Inhibiting ERK phosphorylation stimulated the chemosensitizing effect of curcumin to cisplatin by targeting FEN1. These data reveal that FEN1 overexpression promotes cisplatin resistance, and suggest FEN1 could be a potential therapeutic target to relieve cisplatin resistance in breast cancer. We also demonstrated that curcumin sensitizes breast cancer cells to cisplatin through FEN1 down-regulation.
Keywords: ERK; FEN1; breast cancer; cisplatin resistance; curcumin.