文献类型：期刊文献

英文题名：Fangchinoline suppresses conjunctival melanoma by directly binding FUBP2 and inhibiting the homologous recombination pathway

作者：Bao, Keting[1];Li, Yongyun[2];Wei, Jinlian[1];Li, Ruoxi[1];Yang, Jie[2];Shi, Jiahao[2];Li, Baoli[1];Zhu, Jin[1];Mao, Fei[1];Jia, Renbing[2];Li, Jian[1,3,4]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[2]Shanghai Jiao Tong Univ, Peoples Hosp 9, Sch Med, Dept Ophthalmol, Shanghai 200001, Peoples R China;[3]Dali Univ, Coll Pharm & Chem, 5 Xue Ren Rd, Dali 671000, Yunnan, Peoples R China;[4]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2021

卷号：12

期号：4

外文期刊名：CELL DEATH & DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000638225300007)】；

基金：This work was supported by grants from the National Natural Science Foundation of China (81872747, 21672064), the Innovative Research Team of High-level Local Universities in Shanghai, the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), the National Natural Science Foundation of China (82003603) and the National Mega-project for Innovative Drugs of China (2019ZX09721001-004-003).

语种：英文

摘要：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 significantly inhibit the growth of 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 efficacy 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.