Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53
Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53
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白杨素与顺铂联合上调p53促进Hep G2细胞凋亡
DOI：
10.1016/j.cbi.2015.03.003
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发表时间：
2015-05-05
影响因子：
5.1
通讯作者：
Zou, Fei
中科院分区：
文献类型：
--
作者：
Li, Xin;Huang, Jun-Ming;Zou, Fei
顺铂是一种常用的化疗药物，但其耐药性的存在对顺铂在肿瘤治疗中的临床应用构成了重大挑战。白杨素是一种广泛存在于各种植物和食品中的天然黄酮类化合物，近年来的研究表明它具有有效的抗癌活性。在本研究中，我们发现白杨素和顺铂的组合显着增强Hep G2癌细胞的凋亡。白杨素和顺铂联合应用可通过激活ERK 1/2增加Hep G2细胞中p53的磷酸化和积聚，导致促凋亡蛋白Bax和DR 5的过表达和抗凋亡蛋白Bcl-2的抑制。此外，白杨素和顺铂联合应用不仅通过激活caspase-8促进Hep G2细胞的外源性凋亡，而且通过增加细胞色素c的释放和激活caspase-9促进Hep G2细胞的内源性凋亡。我们的研究结果表明，白杨素和顺铂的组合是一个很有前途的策略化疗的人类癌症是耐顺铂。(C)由Elsevier爱尔兰有限公司出版。
Cisplatin is a chemotherapy drug commonly used for the treatment of human cancers, however, drug resistance poses a major challenge to clinical application of cisplatin in cancer therapy. Recent studies have shown that chrysin, a natural fiavonoid widely found in various plants and foods, demonstrated effective anti-cancer activity. In the present study, we found that the combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells. Combination of chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the antiapoptotic protein BcI-2. In addition, combination of chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells. Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin. (C) 2015 Published by Elsevier Ireland Ltd.