Alpha-tocopheryl succinate enhances doxorubicin-induced apoptosis in human gastric cancer cells via promotion of doxorubicin influx and suppression of doxorubicin efflux
Alpha-tocopheryl succinate enhances doxorubicin-induced apoptosis in human gastric cancer cells via promotion of doxorubicin influx and suppression of doxorubicin efflux
复制标题
α-生育酚琥珀酸酯通过促进阿霉素流入和抑制阿霉素流出来增强阿霉素诱导的人胃癌细胞凋亡
DOI：
10.1016/j.canlet.2011.04.001
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发表时间：
2011-08-28
期刊：
影响因子：
9.7
通讯作者：
Wu, Kun
中科院分区：
文献类型：
--
作者：
Zhang, Xuguang;Peng, Xiangwen;Wu, Kun
阿霉素(Doxo)是一种化疗药物，临床上广泛用于治疗多种癌症。然而，由于耐药性和毒性，治疗最终失败。因此，需要一种联合策略来提高DOXO的疗效和降低其毒性。α-生育酚琥珀酸酯(α-TOS)在体外和体内均显示出抗癌作用。在此，我们报道了Doxo+α-TOS协同诱导SGC-7901细胞凋亡的作用。α-TOS通过促进Doxo内流和抑制Doxo外流来提高Doxo的细胞水平。Doxo诱导的MDR1mRNA和蛋白表达和α-TOS抑制这一事件，表明α-TOS通过抑制MDR1而抑制Doxo外流。Doxo+α-TOS联合作用诱导Fas和Bax蛋白表达增加，caspase-8和caspase-9裂解，提示联合作用可诱导Fas/caspase-8和Bax介导的线粒体依赖性细胞凋亡。综上所述，我们的结果表明，α-TOS通过促进Doxo内流和抑制MDR-1介导的Doxo外流来增强Doxo的抗癌效率。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Doxorubicin (DOXO), a chemotherapy drug, is widely used in clinic for treating a variety of cancers. However, the treatment eventfully fails due to drug resistance and toxicity. Therefore, a combination strategy is needed to increase efficacy and reduce toxicity of DOXO. alpha-tocopheryl succinate (alpha-TOS) exhibits anticancer actions in vitro and in vivo. Here, we reported that combination of DOXO + alpha-TOS cooperatively acted to induce apoptosis in SGC-7901 cells. alpha-TOS enhanced cellular level of DOXO via promotion of DOXO influx and suppression of DOXO efflux. DOXO induced MDR1 mRNA and protein expression and alpha-TOS inhibited this event, indicating that alpha-TOS suppressed DOXO efflux via inhibition of MDR1. Furthermore, combination of DOXO + alpha-TOS induced increased levels of Fas and Bax protein expression and cleavage of caspase-8 and caspase-9, suggesting that combination treatment induced Fas/caspase-8 and Bax mediated mitochondria dependent apoptosis. Taken together, our results demonstrated that alpha-TOS enhanced DOXO anticancer efficiency via promotion of DOXO influx and suppression of MDR-1 mediated DOXO efflux. (C) 2011 Elsevier Ireland Ltd. All rights reserved.