Growth inhibitory effects of dihydroartemisinin on pancreatic cancer cells: involvement of cell cycle arrest and inactivation of nuclear factor-κB
Growth inhibitory effects of dihydroartemisinin on pancreatic cancer cells: involvement of cell cycle arrest and inactivation of nuclear factor-κB
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DOI：
10.1007/s00432-009-0731-0
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发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Xue, Dongbo
中科院分区：
文献类型：
--
作者：
Chen, Hua;Sun, Bei;Xue, Dongbo
在最近的出版物中，我们已经表明，双氢青蒿素（DHA），抗疟疾药物青蒿素的衍生物，抑制胰腺癌细胞的生长在体外和体内介导的抗增殖和促凋亡作用。细胞凋亡可能是由于细胞周期阻滞引起的，转录因子核因子-κ B在细胞凋亡中起重要作用。NF-κ B（NF-kappa B）在胰腺癌细胞凋亡中起重要作用，我们将我们的研究扩展到研究DHA对细胞周期进程和NF-κ B的影响。通过测定胰腺癌细胞中的κ B活性，进一步揭示DHA对胰腺癌的抗癌作用。染色和流式细胞术。Western blot分析检测细胞周期相关蛋白表达的变化。DHA可诱导G 0/G1细胞周期阻滞，并可调节细胞周期蛋白cyclin E、cdk 2、cdk 3、cdk 4、cdk 6、cdk 8、cdk 10、cdk 11、cdk 12、cdk 13、cdk 14、cdk 16、cdk 18、cdk 19和cdk 19的表达。cdk 4和p27（Kip 1）在胰腺癌BxPC-3和AsPC-1细胞中的表达。DHA对胰腺癌细胞NF-κ B的转运和DNA结合活性有剂量依赖性的抑制作用，提示DHA对胰腺癌细胞具有失活作用，结合我们以前的观察，我们的研究结果表明DHA诱导胰腺癌细胞周期阻滞和凋亡，这种作用可能是通过抑制NF-κ B信号通路实现的。我们认为，DHA可以开发为一种新的药物对胰腺癌。
In a recent publication, we have shown that dihydroartemisinin (DHA), a derivative of antimalaria drug artemisinin, inhibits growth of pancreatic cancer cells in vitro and in vivo mediated by its anti-proliferative and pro-apoptotic effects. As it has been shown that the apoptosis might be induced due to cell cycle arrest, and that transcriptional factor nuclear factor-kappa B (NF-kappa B) plays vital roles in the apoptosis of pancreatic cancer cells, we extend our study to investigate the effects of DHA on cell cycle progression and NF-kappa B activity in pancreatic cancer cells to further reveal the anticancer effects of DHA on pancreatic cancer.Cell cycle progression was determined by propidium iodide staining and flow cytometry. Changes in the expression of cell cycle-associated proteins were detected using Western blot analysis. Measurement of NF-kappa B activity was performed with immunoblot analyzing the nuclear protein expression of NF-kappa B/p65 and ELISA detecting the NF-kappa B DNA-binding activity.The treatment with DHA resulted in a dose-dependent G(0)/G(1) cell cycle arrest and regulated the expression of some cyclins, cdks and cdk inhibitors that involved in the G(0)/G(1) cell cycle progression such as cyclin E, cdk2, cdk4 and p27(Kip1) in pancreatic cancer BxPC-3 and AsPC-1 cells. The translocation and DNA-binding activity of NF-kappa B were inhibited in DHA-treated cells in a dose-dependent manner, indicated the inactivation effects of DHA in pancreatic cancer cells.Together with our previous observations, our data show that DHA induces cell cycle arrest and apoptosis in pancreatic cancer cells, and this effect might be due to inhibition of NF-kappa B signaling. We suggest that DHA could be developed as a novel agent against pancreatic cancer.