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Cell Death & Disease

发布日期:2021-09-27 16:49:04 【关闭】
摘要:


期刊名:Cell Death & Disease
网站:https://doi.org/10.1038/s41419-021-03653-4
发表日期:07 April 2021

Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway
Abstract
Conjunctival melanoma (CM) is a rare and fatal ocular tumour with poor prognosis. There is an urgent need of effective therapeutic drugs against CM. Here, we reported the discovery of a novel potential therapeutic target for CM.
Through phenotypic screening of our in-house library, fangchinoline was discovered to signifificantly inhibit the growthof CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1. Further mechanistic experiments indicated that
fangchinoline suppressed the homologous recombination (HR)-directed DNA repair by binding with far upstream element binding protein 2 (FUBP2) and downregulating the expression of HR factors BRCA1 and RAD51. In vitro and
in vivo antitumour experiments revealed that fangchinoline increased the effificacy of cisplatin by blocking HR factors and reduced the drug dose and toxicity. In conclusion, our work provides a promising therapeutic strategy for the
treatment of CM that is worthy of extensive preclinical investigation.
 

Fangchinoline (98%) was from Chengdu DeSiTe Biological Technology Co., Ltd ( Chengdu, China).