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阿司匹林抗癌机理揭秘

已有 4426 次阅读 2014-7-6 05:55 |个人分类:期刊论文|系统分类:论文交流| 阿司匹林

阿司匹林具有抗炎作用,最早被用作解热镇痛药,后来也被用作抗风湿药。它还能抑制血小板凝集,常用来预防缺血性心脏病。

早在1990年代,人们就知道,长期服用低剂量阿司匹林,可以降低癌症风险。比如,阿司匹林可使结直肠癌的发生率下降40%。可是,一直不清楚其机理是什么?

最近,瑞士巴塞尔大学的研究人员在美国《国家癌症研究所杂志》(JNCI)上发表文章,揭示阿司匹林的抗癌机理是能保持稳定的表观遗传特征(F. Noreen, et al. Modulation of Age- and Cancer-Associated DNA Methylation Changes in the Healthy Colon by


Aspirin and Lifestyle. J Nat Cancer Institute, 2014; 106 (7): dju161)。


DNA甲基化模式改变被认为是一种衰老标识,像年龄增长一样,抽烟也能促进衰老,故可以影响DNA甲基化程度。相反,阿司匹林能保持DNA甲基化不变,从而减少衰老致癌性。

研究发现,在20025个CpG位点上,1713个(包括癌症相关甲基化位点)随年龄增长而被甲基化,而服用阿司匹林(两年以上)或接受激素替代疗法的人(50岁以上),这些位点上则较少甲基化。年轻的吸烟者(20年以上)及体质指数(BMI)为25kg/m2以上的人,这些位点上的甲基化程度均与老人一样高。

去年《美国医学会刊》(JAMA)曾发表文章指出,阿司匹林仅能降低野生型BRAF基因携带者的结直肠癌风险,而对突变型BRAF基因携带者无效(Nishihara R, et al. Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status. JAMA, 2013; 309 (24): 2563-2571 DOI: 10.1001/jama.2013.6599)。

前不久,《欧洲药理学报》发表一篇文章,发现阿司匹林在体内转变成水杨酸并分解成二羟基苯甲酸后,可以释放出过氧化氢,而过氧化氢能够通过一系列步骤诱导SIRT1/PGC-1基因,由此影响线粒体代谢与能量利用(P. Kamble, et al. Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin 1/PGC-1 genes. Eur J Pharmacol, 2013; 699: 55-61)。

我曾在1996年阅读过一篇Science文章,发现水杨酸是过氧化氢酶的抑制剂,结果能提高细胞的过氧化氢水平,这与上述阿司匹林释放过氧化氢的发现“异曲同工”。


情坎(冷漠)


一百个放心(张津涤)


Cancer risk: Aspirin and smoking affect aging of genes

Date:
July 1, 2014
Source:
Universität Basel
Summary:
The risk of developing cancer increases with age. Outside factors can affect that risk, like smoking, which increases cancer risk, and regular aspirin use, which has been shown to decrease it. Now researchers have demonstrated the change in risk connected to colorectal cancer with regard to aspirin use. Numerous studies have confirmed the protective effect of the drug against different types of cancer, including reducing the risk to develop colorectal cancer by an average of 40%. However, it is unknown how exactly the drug influences the cancer risk.


Our lifestyle choices affect the aging processes of our genome which can cause cell transformation and cancer.
Credit: Martin Oeggerli / Micronaut, in cooperation with FHNW

The risk of developing cancer increases with age. Factors like smoking and regular aspirin use also affect the risk of cancer -- although in the opposite sense. Researchers from the University of Basel were now able to show that aspirin use and smoking both influence aging processes of the female genome that are connected to colorectal cancer. The Journal of the National Cancer Institute has published their results.

Already in the 1990s, scientists discovered that regular use of aspirin over long periods of time decreases the cancer risk. Since then, numerous studies have confirmed the protective effect of the drug against different types of cancer. Regular aspirin use is said to reduce the risk to develop colorectal cancer by an average of 40%. However, it is unknown how exactly the drug influences the cancer risk.

A research group led by Prof. Primo Schär, molecular geneticists at the Department of Biomedicine from the University of Basel and gastrointestinal specialist PD Dr. Kaspar Truninger, has now discovered a possible mechanism of how aspirin decreases the risk of cancer: It slows down certain aging processes of the genome -- namely modifications that also play an important role in the development of tumors.

In order to analyze the relationships between lifestyle and genome aging, the researchers examined intestinal tissue samples of 546 healthy women over 50 years of age. They compared age-specific changes of gene markers, so-called DNA methylations, with the women's lifestyle factors regarding aspirin use, smoking, body mass index and hormonal replacement therapy. The most significant effects were measured for aspirin use and smoking.

Aging Markers

"Each cell's genome resembles a library that is full of bookmarks," explains Schär. Thanks to these bookmarks, the cells know which genes to read, so that they can fulfill their specialized tasks as skin, muscle or intestinal cells. "But these markers are not very stable and change during the course of age. If, at certain parts of the genome, the change is to drastic, tumors can develop," says Schär.

In this study, the researchers were able to show for the first time that this age-related decay of gene markers can be slowed down by the regular use of aspirin. Smoking on the other hand, accelerates the aging process. "Especially affected are genes that also play a role in the development of cancer," says Dr. Faiza Noreen, research associate at the Department of Biomedicine from the University of Basel and first author of the study.

Truninger emphasizes that it would be premature to start taking aspirin solely for cancer prevention without consulting a doctor first -- especially when regarding the potential side effects such as gastrointestinal bleeding.

Story Source:

The above story is based on materials provided by Universität Basel. Note: Materials may be edited for content and length.

Journal Reference:

  1. F. Noreen, M. Roosli, P. Gaj, J. Pietrzak, S. Weis, P. Urfer, J. Regula, P. Schar, K. Truninger. Modulation of Age- and Cancer-Associated DNA Methylation Change in the Healthy Colon by Aspirin and Lifestyle. JNCI Journal of the National Cancer Institute, 2014; 106 (7): dju161 DOI: 10.1093/jnci/dju161








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