二氢青蒿素在体外和体内均可使 NF-κB 失活，并增强吉西他滨对胰腺癌的抗肿瘤作用。

Dihydroartemisinin inactivates NF-kappaB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.

出版信息

Cancer Lett. 2010 Jul 1;293(1):99-108. doi: 10.1016/j.canlet.2010.01.001. Epub 2010 Feb 4.

DOI:10.1016/j.canlet.2010.01.001

PMID:20137856

Abstract

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-kappaB 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-kappaB activity and its related gene products, and predictably, significantly reduced tumor volume. We concluded that inhibition of gemcitabine-induced NF-kappaB activation is one of the mechanisms that DHA dramatically promotes its anti-tumor effect on pancreatic cancer.

摘要

吉西他滨是目前胰腺癌最常用的化疗药物，但随着时间的推移，肿瘤会重新出现获得性耐药，这成为所有与吉西他滨相关化疗的主要问题。在这项研究中，我们首次证明二氢青蒿素（DHA）可增强吉西他滨诱导的体外 BxPC-3 和 PANC-1 细胞系生长抑制和凋亡。其机制至少部分是由于 DHA 失活了吉西他滨诱导的 NF-κB 激活，从而极大地降低了其靶基因产物的表达，如 c-myc、细胞周期蛋白 D1、Bcl-2、Bcl-xL。在我们的体内研究中，当与 DHA 联合使用时，吉西他滨也表现出显著增强的抗肿瘤作用，表现为明显增加的凋亡，以及降低 Ki-67 指数、NF-κB 活性及其相关基因产物，并且可以预测，肿瘤体积显著缩小。我们得出结论，抑制吉西他滨诱导的 NF-κB 激活是 DHA 显著增强其对胰腺癌抗肿瘤作用的机制之一。