Session: Analytical Division Poster:

Neuroblastoma is a solid, intractable, extracranial, pediatric tumor 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, the dose-dependent responses of neuroblastoma cells to anticancer drugs in various microenvironments have not been fully explored. Here, we investigated the effects of different topotecan concentrations on human neuroblastoma cells (SK-N-SH, SH-SY5Y, and SK-N-BE) under varying nutrient supply conditions. Reduced toxicity was observed from the serum-starved human neuroblastoma cells, and 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 of SK-N-SH cells, we showed that topotecan (1 μM) upregulated DNA repair and cholesterol-mediated topotecan efflux, resulting in topotecan resistance. Cell cycle analysis and quantitative analysis of membrane cholesterol further supports our network analysis based on quantitative proteomics. Our results provide a model for high-dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.

Sang-Won Lee

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