The computational model of P53 regulatory circuit manipulation in cancer therapy: The new hope of targeted drug remedy

P53 is tumor suppressor gene that plays important roles in regulating cell cycles in human including cell cycles arrest(inhibit cellular growth) and cell death[l]. It can be triggered by damaged DNA, ionizing agents or oxidative stress via transcription process". After p53 IS triggered, it is called "p53 transcription factor". The function of p53 transcription factor is related to programmed cell death or cellular apoptosis by manipulating other pro-apoptotic factors to induce cell death. High level of p53 transcription factor leads to cell death. Mutation in p53 gene leads to abnormality in cellular growth and development of cancers [2]. P53 is complicated pathway there are involved in many regulatory genes such as Mdm2 and Arf through controlling its level[l]. The objective of this study is to complete the information about p53 dynamics regulatory circuit and to assist in searching for new strategies to increase p53 transcription factors as new chemotherapeutics. The computational simulation was proposed mathematical equations as the same as [3] but this model was considered only 4 genes including p53, DYRK2, Mdm2 and p14Arf. These equations were applied to biliary cancer and were adjusted 30 percent of their kinetic parameters[4]. The results showed that the combination of p53, Mdm2 and p14Arf was the most decreasing in p53 total level about 44.83 percent compared to normal and other mutation genes. Compared to other drugs, the combination of p53, Mdm2 and p14Arf drug is the most effective drug that increases 80.98 percent of p53 total level among of genes mutation.