bioluminescence-based high-throughput screen identifies pharmacological agents that target neurotransmitter signaling in small cell lung carcinomabioluminescence-based筛选确定药物这一目标在小细胞肺癌神经递质信号.pdf

Bioluminescence-Based High-Throughput Screen Identifies Pharmacological Agents That Target Neurotransmitter Signaling in Small Cell Lung Carcinoma Ma. Reina D. Improgo, Christopher W. Johnson, Andrew R. Tapper, Paul D. Gardner* Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America Abstract Background: Frontline treatment of small cell lung carcinoma (SCLC) relies heavily on chemotherapeutic agents and radiation therapy. Though SCLC patients respond well to initial cycles of chemotherapy, they eventually develop resistance. Identification of novel therapies against SCLC is therefore imperative. Methods and Findings: We have designed a bioluminescence-based cell viability assay for high-throughput screening of anti-SCLC agents. The assay was first validated via standard pharmacological agents and RNA interference using two human SCLC cell lines. We then utilized the assay in a high-throughput screen using the LOPAC1280 compound library. The screening identified several drugs that target classic cancer signaling pathways as well as neuroendocrine markers in SCLC. In particular, perturbation of dopaminergic and serotonergic signaling inhibits SCLC cell viability. Conclusions: The convergence of our pharmacological data with key SCLC pathway components reiterates the importance of neurotransmitter signaling in SCLC etiology and points to possible leads for drug development. Citation: Improgo MRD, Johnson CW, Tapper AR, Gardner PD (2011) Bioluminescence-Based High-Throughput Screen Identifies Pharmacological Agents That Target Neurotransmitter Signaling in Small Cell Lung Carcinoma. PLoS ONE 6(9): e24132. doi:10.1371/journal.pone.0024132 Editor: Joseph Najbauer, City of Hope National Medical Center and Beckman Research Institute