Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway

发布时间：2022-08-22

作者：乐美天标准品

阅读次数：4623

文章字数：1021

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).

原文链接：https://doi.org/10.1038/s41419-021-03653-4

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Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway

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