Regulation of p53 by siRNA in radiation treated cells: Simulation studies

• Autorzy: Krzysztof Puszyński , Roman Jaksik , Andrzej Świerniak
• Języki publikacji: EN

Abstrakty

EN

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.

Słowa kluczowe

EN

siRNA; p53; combined therapy

• Wydawca: University of Zielona Gora Press
• Czasopismo: International Journal of Applied Mathematics and Computer Science
• Rocznik: 2012
• Tom: 22
• Numer: 4
• Strony: 1011-1018

Daty

wydano

2012

otrzymano

2012-01-26

poprawiono

2012-05-17

Twórcy

autor

Krzysztof Puszyński

• Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland

autor

Roman Jaksik

• Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland

autor

Andrzej Świerniak

• Institute of Automatic Control, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland

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Identyfikatory

DOI

10.2478/v10006-012-0075-9