利用斑馬魚胚胎篩選抑制體表色素生成的藥物

Using Pigmentation as a Parameter to Screen Drugs that Inhibits Skin Pigmentation in Zebrafish

楊博熙(Bo-Xi Yang) ； 許惠真(Hwei-Jan Hsu) ； 王文德(Wen-Der Wang)

《化學》 73卷3期 (2015/09) Pp. 201-208

https://doi.org/10.6623/chem.2015021

摘要

傳統的藥物開發策略是以細胞模式，選擇性地瞄準特定的分子為重點。但大多數藥物在細胞研究結果常無法在動物模式有良好的再現性。近年來斑馬魚取代細胞模式成為一個脊椎動物模型用於評估藥物作用。體表黑色素細胞是形成皮膚顏色的一部份，其功能可用來保護人體以免受到陽光中紫外線的傷害。體表黑色素細胞是由胚胎時期的神經及幹細胞衍生而來。體表黑痣和黑色素細胞瘤則是黑色素細胞異常增生所導致。本研究以斑馬魚胚胎黑色素形成為指標，在2404種藥物中篩選出6種具有抑制黑色素生成的藥物。其中更以4657-F4具有良好的抑制色素形成、低使用劑量與低毒性等特性。相信以此藥物篩選模式策略，未來可以篩選出更多高效率與低毒性的藥物。

關鍵字

斑馬魚 ； 藥物篩選 ； 黑色素細胞

並列摘要

The traditional strategy of drug discovery is focus onthe selectively target on the cell model. Many lines of evidence that the responsive phenomena of the drugs on cell model mostly do not represent on animal models. In recent years, zebrafish are becoming a popular vertebrate model organism for drug screening and discovery. The melanophores on skin are the melanin-containing pigment cells as a shield against further damage from UV radiation. The melanophores are derived from neural stem cells during embryogenesis. Misregulation of melnophore proliferation causes melanoma. In this study, we performed a chemical screen in which embryos were treated with approved oncologenic drugs or synthetic compounds and screen for compounds that affect skin pigmentation. We 6 of 2404 drugs have been found to inhibit skin pigmentation in zebrafish. Our study reveals that 4657-F4 chemical exhibits more effective effect on the inhibition of skin pigmentation and low embryonic toxicity than other 5 chemicals and PTU.

並列關鍵字

Zebrafish ； Drug screening ； Melanophore