文章基本信息

标题：Regulation of p53 by siRNA in radiation treated cells: Simulation studies
本地全文：下载
作者：Krzysztof Puszyński ; Roman Jaksik ; Andrzej Świerniak 等
期刊名称：International Journal of Applied Mathematics and Computer Science
电子版ISSN：2083-8492
出版年度：2012
卷号：22
期号：4
DOI：10.2478/v10006-012-0075-9
出版社：De Gruyter Open
摘要：Ionizing radiation activates a large variety of intracellular mechanisms responsible for maintaining appropriate cell functionality or activation of apoptosis which eliminates damaged cells from the population. The mechanism of such induced cellular death is widely used in radiotherapy in order to eliminate cancer cells, although in some cases it is highly limited by increased cellular radio-resistance due to aberrations in molecular regulation mechanisms of malignant cells. Despite the positive correlation between the radiation dose and the number of apoptotic cancer cells, radiation has to be limited because of extensive side effects. Therefore, additional control signals whose role will be to maximize the cancer cells death-ratio while minimizing the radiation dose and by that the potential side effects are worth considering. In this work we present the results of simulation studies showing possibilities of single gene regulation by small interfering RNA (siRNA) that can increase radio-sensitivity of malignant cells showing aberrations in the p53 signaling pathway, responsible for DNA damage-dependant apoptosis. By blocking the production of the p53 inhibitor Mdm2, radiation treated cancer cells are pushed into the apoptotic state on a level normally achievable only with high radiation doses. The presented approach, based on a simulation study originating from experimentally validated regulatory events, concerns one of the basic problems of radiotherapy dosage limitations, which, as will be shown, can be partially avoided by using the appropriate siRNA based control mechanism
关键词：siRNA; p53; combined therapy