Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition
Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition
复制标题
大黄素对胰腺癌中吉西他滨作用的增强与生存素抑制有关
DOI：
10.1016/j.bcp.2009.02.021
复制
发表时间：
2009-06-01
影响因子：
5.8
通讯作者：
Wu, Yulian
中科院分区：
文献类型：
--
作者：
Guo, Qingqu;Chen, Ying;Wu, Yulian
胰腺癌是一种对吉西他滨化疗具有耐药性的恶性肿瘤。本研究发现中药有效成分大黄素可增强吉西他滨诱导的胰腺癌细胞凋亡。Survivin是凋亡抑制基因家族的成员，参与细胞分裂和凋亡抑制，是β-catenin/Tcf/Lef的靶基因。Western blot和PCR分析表明大黄素抑制survivin的表达，在密切和时间依赖性的方式。我们进一步证实了生存素的表达可以被吉西他滨上调。令人惊讶的是，吉西他滨诱导的生存素表达可以与大黄素治疗组合抑制。此外，用吉西他滨和大黄素处理的细胞显示出β-连环蛋白的优先质膜周围位置，阻断了吉西他滨诱导的β-连环蛋白向细胞核的移位。除了这些体外结果，我们还发现大黄素通过下调生存素和β-连环蛋白的表达增强吉西他滨的体内抗肿瘤作用。综上所述，这些结果表明大黄素通过抑制胰腺癌中的生存素基因而增强吉西他滨的抗肿瘤活性。(c)2009爱思唯尔公司All rights reserved.
Pancreatic cancer is one human malignancy which has chemoresistant behavior to gemcitabine treatment. In this study, we revealed that emodin, an active component from Chinese medicinal herbs, could enhance pancreatic cancer cells apoptosis induced by gemcitabine. Survivin, a member of the inhibitor of apoptosis gene family, is involved in control of cell division and inhibition of apoptosis and described as a beta-catenin/Tcf/Lef target gene. Western blot and PCR analysis showed that emodin suppressed survivin expression in a close- and time-dependent manner. We further demonstrated survivin expression could be up-regulated by gemcitabine. Surprisingly, survivin expression induced by gemcitabine could be inhibited in combination with emodin treatment. Moreover, cells treated with gemcitabine and emodin showed a preferential peri-plasma membrane position of beta-catenin, blocking the translocation of beta-catenin to nucleus induced by gemcitabine. In addition to these in vitro results, we also found that emodin potentiates the antitumor effects of gemcitabine in vivo by down-regulating the expression of survivin and beta-catenin. Taken together, these results suggest that emodin potentiates gemcitabine antitumor activity through suppression of survivin gene in pancreatic cancer. (c) 2009 Elsevier Inc. All rights reserved.