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제124회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Uncovering dose-dependent chemoresistance of serum-starved SK-N-SH neuroblastoma cells against the anticancer drug

2019년 8월 28일 14시 19분 13초
ANAL.P-159 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
10월 18일 (금요일) 11:00~12:30
포스터 분석구두발표
Analytical Chemistry
저자 및
Sooyeon Chae, Min Ji Kim, Paul Valery Migisha Ntwali, Chae Eun Heo, Chae Ri Park, MyungKook Son, Hugh I. Kim*
Department of Chemistry, Korea University, Korea
Neuroblastoma is a solid tumor that arises from the sympathetic nervous system with complex, heterogeneous clinical behaviors. Chemotherapy is widely used to treat neuroblastoma and many studies have attempted to decipher the action mechanism of anticancer drugs. however, in spite of complex, heterogeneous of neuroblastoma, chemotherapy regimen is fixed and not consider heterogeneity of tumor cells. In this study, we investigated the effects of different concentration of topotecan on human neuroblastoma SK-N-SH cells under varying nutrient supply conditions. The survival rate of serum-starved SK-N-SH cells increased upon treatment with a high concentration (1 μM) of topotecan. Using quantitative proteomics and network analysis, we showed that topotecan (1 μM) upregulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Time-resolved topotecan quantitation using multiple reaction monitoring mass spectrometry further supports that topotecan resistance was associated with enhanced drug efflux. Our results provide a model for high-dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.