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- W4280532162 abstract "Abstract Few models exist that allow for rapid and effective screening of anti-metastasis drugs. Here, we present a phenotype-based chemical screen utilizing gastrulation of zebrafish embryos for identification of anti-metastasis drugs. Based on our hypothesis that small molecules which interrupt zebrafish gastrulation might suppress metastasis progression of cancer cells, we designed a drug screening concept which uses epiboly, the first morphogenetic movement in gastrulation, as a marker. The screen only needs zebrafish embryos and enables 100 chemicals to be tested in five hours through just observing epiboly progression of a test chemical-treated embryos. In the screen, embryos at two-cell stage are firstly corrected and then developed to sphere stage. The embryos are treated with a test chemical and incubated in the presence of the chemical until vehicle-treated embryos develop to 90% epiboly stage. Finally, positive ‘hit’ chemicals that interrupt epiboly progression are selected through comparing epiboly progression of a test chemical-treated embryos with that of vehicle-treated embryos under a stereoscopic microscope. Previous study subjected 1280 FDA-approved drugs into the screen and identified Adrenosterone and Pizotifen as epiboly-interrupting drugs. Mouse models of metastasis validated that the drugs could suppress metastasis of breast cancer cells. Furthermore, the screen can be diverted to a chemical genetic screening platform for identification of metastasis-promoting genes. Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11b1) and serotonin receptor 2C (HTR2C), which are primary target of Adrenosterone and Pizotifen respectively, induces epithelial-mesenchymal transition (EMT) and promote metastasis of breast cancer cells." @default.
- W4280532162 created "2022-05-22" @default.
- W4280532162 creator A5053287301 @default.
- W4280532162 creator A5060762242 @default.
- W4280532162 creator A5078064404 @default.
- W4280532162 date "2022-05-07" @default.
- W4280532162 modified "2023-09-30" @default.
- W4280532162 title "A zebrafish embryo screen utilizing gastrulation for identification of anti-metastasis drugs" @default.
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