Curcumin increases breast cancer cell sensitivity to cisplatin by decreasing FEN1 expression.
Curcumin increases breast cancer cell sensitivity to cisplatin by decreasing FEN1 expression.
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姜黄素通过降低 FEN1 表达来增加乳腺癌细胞对顺铂的敏感性
DOI：
10.18632/oncotarget.24109
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发表时间：
2018-02-16
期刊：
影响因子：
--
通讯作者：
Chen B
中科院分区：
文献类型：
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作者：
Zou J;Zhu L;Jiang X;Wang Y;Wang Y;Wang X;Chen B
皮瓣核酸内切酶1（FEN 1）过表达促进乳腺癌。我们研究了FEN 1在乳腺癌细胞顺铂耐药和姜黄素化疗增敏作用中的作用。我们证明，FEN1过表达促进乳腺癌细胞的顺铂耐药性，而FEN1敲低增强顺铂敏感性。姜黄素以剂量依赖性方式下调FEN 1表达。顺铂和姜黄素的组合通过在体外和体内下调FEN 1表达来增强乳腺癌细胞对顺铂的敏感性。ERK磷酸化水平的增加促进了乳腺癌细胞对顺铂的耐药和顺铂诱导的FEN 1过表达。抑制ERK磷酸化通过靶向FEN 1刺激姜黄素对顺铂的化学增敏作用。这些数据表明，FEN 1过表达促进顺铂耐药，并建议FEN 1可能是一个潜在的治疗靶点，以减轻乳腺癌顺铂耐药。我们还证明了姜黄素通过下调FEN1使乳腺癌细胞对顺铂敏感。
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.