Dihydroartemisinin inactivates NF-κB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo
Dihydroartemisinin inactivates NF-κB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo
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DOI：
10.1016/j.canlet.2010.01.001
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发表时间：
2010-07-01
期刊：
影响因子：
9.7
通讯作者：
Sun, Bei
中科院分区：
文献类型：
--
作者：
Wang, Shuang-Jia;Gao, Yue;Sun, Bei
吉西他滨是目前最知名的胰腺癌化疗选择，但随着时间的推移，肿瘤会重新出现获得性耐药，这成为所有吉西他滨相关化疗的主要问题。在这项研究中，我们首次证明了双氢青蒿素（DHA）在体外增强吉西他滨诱导的BxPC-3和PANC-1细胞系的生长抑制和凋亡。其机制至少部分是由于DHA使吉西他滨诱导的NF-κ B B活化失活，从而极大地降低其靶基因产物如c-myc、cyclin D1、Bcl-2、Bcl-xL的表达。在我们的体内研究中，当与DHA组合时，吉西巴宾还表现出显著增强的抗肿瘤作用，如通过显著增加的细胞凋亡以及降低的Ki-67指数、NF-κ B活性及其相关基因产物以及可预测的显著减小的肿瘤体积所表现的。我们的结论是，抑制吉西他滨诱导的NF-κ B活化是DHA显著促进其对胰腺癌的抗肿瘤作用的机制之一。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Gemcitabine is currently the best known chemotherapeutic option available for pancreatic cancer, but the tumor returns de novo with acquired resistance over time, which becomes a major issue for all gemcitabine-related chemotherapies. In this study, for the first time, we demonstrated that dihydroartemisinin (DHA) enhances gemcitabine-induced growth inhibition and apoptosis in both BxPC-3 and PANC-1 cell lines in vitro. The mechanism is at least partially due to DHA deactivates gemcitabine-induced NF-kappa B activation, so as to decrease tremendously the expression of its target gene products, such as c-myc, cyclin D1, Bcl-2, Bcl-xL. In our in vivo studies, gemcibabine also manifested remarkably enhanced anti-tumor effect when combined with DHA, as manifested by significantly increased apoptosis, as well as decreased Ki-67 index, NF-kappa B activity and its related gene products, and predictably, significantly reduced tumor volume. We concluded that inhibition of gemcitabine-induced NF-kappa B activation is one of the mechanisms that DHA dramatically promotes its anti-tumor effect on pancreatic cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.