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[R. Organoid-2]



             Comparative proteomic analysis and evaluation of anticancer


                  drug responses using patient-derived tumor organoids




            Yeon-Jin Chu¹˙#, Hyuna Kim¹˙#, Hyeong Ho Cho¹, Ki Soon Kim¹, Donghyun Park¹, Woo Yong Oh¹,
                                                     Yoonsook Lee¹˙*


           ¹Clinical Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology

                                      Administration Comple,  Cheongju 28159, Korea




        Tumor organoids using 3D culture system are well known to reflect the heterogeneity and biological properties of
        patients  compared  with  cancer  cell  lines  using  2D  culture  system.  However,  there  are  few  studies  of  cancer

        mechanism and drug effects using tumor organoids. In this study, we investigated the effects and the alteration of
        proteins by anticancer drug using patient-derived tumor organoids.    At first, we cultured patient-derived tumor

        organoids isolated from colorectal cancer speciemens using matrigel. Each tumor organoids were shown different
        growth properties and proteins expression level. Then, we evaluated the cytotoxicity of 5-Fluorouracil(5-FU) in tumor

        organoids. We found that 5-FU induced cell death was caused by apoptosis through the expression of apoptotic
        proteins. Based on these data, we tried to find proteins associated with 5-FU resistance using 2-dimensional gel

        eletrophoresis(2-DE)  and  MALDI-TOF.  Most of  proteins were  involved  in  metabolism,  synthesis/degradation  of
        protein, cytoskeleton, redox reaction, etc. We measured mRNA and protein levels of them, and selected candidates

        for biomarker of 5-FU resistance. Our data shows that tumor organoids can be useful tool of tumor studies for
        evaluation and investigation of anti-cancer drug.
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