Recent Developments in Healthcare Research for Patients

초록

The Importance of Premature Senescence in Cancer Treatment Jae-Seon Lee, Ph. D. Department of Biomedical Sciences, College of Medicine, INHA University Incheon 400-712, Korea Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. Since a variety of treatments have been shown to trigger premature senescence, senescence has recently become regarded as a general biological program of terminal growth arrest. DNA-damaging agents including ionizing radiation (IR) and chemotherapeutic drugs induce senescent phenotypes in cancer cells. Recent studies suggest that induction of premature senescence is a promising treatment for solid cancers. Our final research goal is to increase the efficacy of cancer therapy via understanding of therapy-induced premature senescence in cancer cells. To achieve our research goal, firstly, we identified cathepsin D and eukaryotic elongation factor 1 as novel senescence biomarkers using comparative proteomic analysis. Secondly, we elucidated molecular mechanism of c-Jun-N-terminal kinase (JNK) inhibitor as a combinational drug for the radiotherapy. We also demonstrated that PTEN-mutated cancer cells underwent premature senescence as a compensatory role for apoptosis due to activation of AKT/ROS/p53/p21 signaling pathway in IR-exposed glioma cells. Lastly, we identified Wig1 as a novel senescence regulatory gene via dictating association of RNA-induced silencing complex (RISC) with p21 mRNA using microarray analysis in IR-induced senescent cancer cells. Conclusively, our results affirm that radiotherapy (RT)-induced premature senescence could be an alternative mechanism of apoptosis-resistant cancer cells, and we expect our findings may aid in the understanding of the clinical significance of premature senescence in radiation-treated cancer cells.