Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.

Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.
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DOI:
10.1007/s11605-012-1869-7
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发表时间:
2012-06
影响因子:
3.2
通讯作者:
McFadden, David
McFadden, David
中科院分区:
医学3区
文献类型:
--
作者:
McCormack, Denise Elizabeth;Mannal, Patrick;McDonald, Debbie;Tighe, Scott;Hanson, Joshua;McFadden, David

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为了研究紫檀芪在胰腺癌中的抑制作用,我们对紫檀芪处理的胰腺癌细胞进行了基因组分析。我们还研究了pterostilbene对致癌标志物锰超氧化物歧化酶,细胞色素C,Smac/DIABLO和STAT 3磷酸化的影响。在体内模型中进一步评价紫檀芪的抗增殖作用。用紫檀芪处理胰腺癌细胞,并用DNA微阵列分析进行评价。使用ELISA分析紫檀芪处理的细胞的细胞色素C、Smac/DIABLO、锰超氧化物歧化酶(MnSOD)/抗氧化活性和STAT 3磷酸化。使用ANOVA对数据进行统计学分析。然后将紫檀芪给予裸鼠8周,记录肿瘤生长率并进行统计学分析。微阵列分析的紫檀芪处理的细胞显示上调促凋亡基因。在体外,紫檀芪治疗改变磷酸化STAT 3,MnSOD/抗氧化活性,细胞色素C和Smac/DIABLO的水平。在裸鼠中,口服紫檀芪抑制肿瘤生长率。Pterostilbene改变胰腺癌的基因表达,并增加抗增殖标志物细胞色素C,Smac/DIABLO和MnSOD/抗氧化活性。它还显示出抑制磷酸化的STAT 3(加速肿瘤发生的标志物)并减少体内胰腺肿瘤生长。进一步的研究是必要的,以阐明在人类的影响紫檀芪。
To investigate the inhibitory role of pterostilbene in pancreatic cancer, we conducted a genomic analysis of pterostilbene-treated pancreatic cancer cells. We also investigated the effect of pterostilbene upon the carcinogenic markers, manganese superoxide dismutase, cytochrome C, Smac/DIABLO, and STAT3 phosphorylation in vitro. The antiproliferative effects of pterostilbene were further evaluated in an in vivo model. Pancreatic cancer cells were treated with pterostilbene and evaluated with DNA microarray analysis. Pterostilbenetreated cells were analyzed for cytochrome C, Smac/DIABLO, manganese superoxide dismutase (MnSOD)/antioxidant activity, and STAT3 phosphorylation using ELISA. Data were statistically analyzed using ANOVA. Pterostilbene was then administered to nude mice for 8 weeks, and tumor growth rates were recorded and statistically analyzed. Microarray analysis of pterostilbene-treated cells revealed upregulation of pro-apoptosis genes. In vitro, pterostilbene treatment altered levels of phosphorylated STAT3, MnSOD/antioxidant activity, cytochrome C, and Smac/DIABLO. In nude mice, oral pterostilbene inhibited tumor growth rates. Pterostilbene alters gene expression in pancreatic cancer and increases the antiproliferative markers cytochrome C, Smac/DIABLO, and MnSOD/antioxidant activity. It was also shown to inhibit phosphorylated STAT3, a marker of accelerated tumorigenesis, and decrease pancreatic tumor growth in vivo. Further studies are warranted to elucidate the effects of pterostilbene in humans.
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