高通量筛选
高含量筛选
药物发现
药品
生物
神经母细胞瘤
药理学
细胞
计算生物学
细胞培养
生物信息学
生物化学
遗传学
作者
Ahlem Zaghmi,Erdem Aybay,Long Jiang,Mei Shang,Julia Steinmetz‐Späh,Fredrik Wermeling,Per Kogner,Marina Korotkova,Päivi Östling,Per‐Johan Jakobsson,Brinton Seashore‐Ludlow,Karin Larsson
标识
DOI:10.1002/1878-0261.13502
摘要
High‐throughput drug screening enables the discovery of new anticancer drugs. Although monolayer cell cultures are commonly used for screening, their limited complexity and translational efficiency require alternative models. Three‐dimensional cell cultures, such as multicellular tumor spheroids (MCTS), mimic tumor architecture and offer promising opportunities for drug discovery. In this study, we developed a neuroblastoma MCTS model for high‐content drug screening. We also aimed to decipher the mechanisms underlying synergistic drug combinations in this disease model. Several agents from different therapeutic categories and with different mechanisms of action were tested alone or in combination with selective inhibition of prostaglandin E 2 by pharmacological inhibition of microsomal prostaglandin E synthase‐1 (mPGES‐1). After a systematic investigation of the sensitivity of individual agents and the effects of pairwise combinations, GFP‐transfected MCTS were used in a confirmatory screen to validate the hits. Finally, inhibitory effects on multidrug resistance proteins were examined. In summary, we demonstrate how MCTS‐based high‐throughput drug screening has the potential to uncover effective drug combinations and provide insights into the mechanism of synergy between an mPGES‐1 inhibitor and chemotherapeutic agents.
科研通智能强力驱动
Strongly Powered by AbleSci AI