J0206-1-5 Systems Biology Modeling of Tumors in Radiotherapy

Abstract

Radiotherapy shrinks solid tumors by irradiating cancer cells. Radiation effects on genes in cancer cells and causes apoptosis or arrest of cell cycle by changing patterns of protein expression. If it is possible to know about the tumor protein and enzyme reactions, more effective treatment would be performed. In this study, based on the concept of systems biology, we aimed to simulate the reaction mechanism of cancer cells in cell cycle to radiotherapy. Main agents of cell cycle machinery are cyclin, cyclin dependent kinase (CKI) and CDK inhibitor (CKI). Various cyclins are produced in each of cell cycle phases and configure complexes with particular CDK. These complexes promote cell cycle. Meanwhile, CKIs inhibit cell cycle by inactivating the cyclin-CDK complexes. This study modeled interactions among these agents and simulated sequential progression of cell cycle in normal cells. Based on the normal cell cycle model, cancer cell cycle model and radiotherapy model were constructed by modifying expressions of control agents. Simulation results showed that each cyclin-CDK complex was activated at appropriate time in normal cell cycle model, suggesting that cell cycle proceeded properly. In radiotherapy model, cell cycle did not progress because particular cyclin-CDK complexes did not progress due to expression of p53 gene. From the above results, the model proposed here seems to be suitable to simulate cell cycle progress.