2015 Fiscal Year Annual Research Report
Enhancing apoptosis of cancers using systems biology approach.
| Project/Area Number |
25430184
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| Research Institution | Keio University |
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Principal Investigator |
Selvarajoo Kumar 慶應義塾大学, 政策・メディア研究科, 准教授 (40439253)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | TRAIL / Cancer / Computational Model / Apoptosis / Tumor Immunology |
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| Outline of Annual Research Achievements |
Over the last decade, our research team has investigated the dynamic responses and global properties of living cells using systems biology approaches. For this project, we focused on overcoming cancer resistance. TRAIL (tumor necrosis factor related apoptosis-inducing ligand), a proinflammatory cytokine, has shown promising success in controlling cancer threat due to its ability to induce apoptosis in cancers specifically, while having limited effect on normal cells. Nevertheless, several malignant cancer types, such as fibrosarcoma (HT1080) or colorectal adenocarcinoma (HT29), remain non-sensitive to TRAIL. To sensitize HT1080 to TRAIL treatment, we developed a dynamic computational model based on perturbation-response approach, to predict a crucial co-target to enhance cell death. The model simulations suggested that PKC inhibition together with TRAIL induce 95% cell death. Subsequently, we confirmed this result experimentally utilizing the PKC inhibitor, bisindolylmaleimide (BIM) I, and PKC siRNAs in HT1080.
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Research Products
(4 results)
