A high-throughput screen identifies inhibitors of lung cancer stem cells - 17/06/21
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Abstract |
Metastasis is the main cause of cancer morbidity and mortality. Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that can drive metastasis. The identification of CSC inhibitors and CSC-related genes is an alluring strategy for suppressing metastasis. Here, we established a simple and repeatable high-throughput CSC inhibitor screening platform that combined tumor sphere formation assays and cell viability assays. Human lung cancer cells were cocultured with 1280 pharmacologically active compounds (FDA-approved). Fifty-four candidate compounds obtained from our screening system completely or partially inhibited tumor sphere formation. A total of 5 of these 54 compounds (prochlorperazine dimaleate, thioridazine hydrochloride, ciproxifan hydrochloride, Ro 25-6981 hydrochloride, and AMN 082) completely inhibited the self-renewal of CSCs without cytotoxicity in vitro via their targets and suppressed lung cancer metastasis in vivo, suggesting that our screening platform is selective and reliable. DRD2, HRH3, and GRIN2B exhibited potent genes promoting CSCs in vitro experiments and clinical datasets. Further validation of the top hit (DRD2) and previously published studies demonstrate that our screening platform is a useful tool for CSC inhibitor and CSC-related gene screening.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | A high-throughput screening platform was developed to identify CSC inhibitors. |
• | Five compounds identified from the screening platform inhibit lung cancer metastasis. |
• | CSC-related genes can be identified from the screening platform. |
Abbreviations : CSCs, MICs, GPCRs, TL, DRD2, HRH3, GRIN2B, GRM7, DR, Facs, ATCC, ECACC, STR, SPF, NANOG, SOX2, SOX9, OCT4, TAZ, GEO, NCBI, PKC, ECM, HR, FDA, AML, MFI, TMA
Keywords : High-throughput, Screen, Laser scanning microplate technology, Lung cancer stem cells, Metastasis
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Vol 140
Article 111748- août 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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