摘要
目的高通量筛选技术筛选抑制肝癌(PLC)细胞生长的新型小分子化合物。方法将PLC HepG2、Huh7细胞进行培养,培养后用于实验。选择3个小分子化合物数据库(合计3272个小分子化合物),分别为Prestwick、Tocriscreen、Selleck Chem。以及进行高通量筛选和靶化合物的筛选。结果本研究从3272个小分子化合物中利用高通量筛选技术选出抑制PLC细胞生长的目的化合物(hits)。初筛出的hits为z-score<-1.5,差异有统计学意义( P <0.05)。本研究通过比较9块化合物筛选板2种PLC细胞系(HepG2、Huh7)的重叠区域,共筛选出31种能够同时抑制这2个细胞系生长,且z-score<-1.5的化合物。最终筛选出36种hits化合物,包括5种临床治疗PLC的常用化疗药物和分子式。阿霉素作为hits被2次筛选出来,故最终初筛成功的新型化合物共有31种。结论通过高通量筛选技术筛选出31种可能具有抑制PLC细胞生长作用的新型小分子化合物,且有可能成为PLC治疗中的新型靶向药物。
Objective To screen novel small molecular weight compounds for inhibiting the growth of primary liver cancer(PLC) cells using the high throughput technology. Methods PLC HepG2 and Huh7 cells were cultured for high throughput screening from the Prestwick,Tocriscreen and Selleck Chem libraries. Results The hits that inhibited PLC cell growth were selected from 3272 small molecular weight compounds,and the z-score for initial hits screening was <-1.5( P <0.05).A total of 31 hits(z-score <-1.5) that could simultaneously inhibit the growth of two PLC cell lines(HepG2 and Huh7) were screened out by comparing the overlapping regions of 9 screening plates.Finally,36 kinds of hits compounds were screened out,including 5 commonly used chemotherapeutic drugs and molecular formulas for clinical treatment of PLC.Adriamycin was screened out twice.Therefore,31 hits were selected finally. Conclusion Thirty-one novel small molecular weight compounds with the potential ability to inhibit the growth of PLC cells were successfully selected as the new targeted drugs by the high throughput technology.
作者
何星星
谢步善
刘建国
郭贵海
HE Xing-xing;XIE Bu-shan;LIU Jian-guo;GUO Gui-hai(Department of Gastroenterology,the First Affiliated Hospital ofNanchang University,Nanchang 330006,China)
出处
《南昌大学学报（医学版）》
CAS
2019年第2期1-4,共4页
Journal of Nanchang University：Medical Sciences
基金
国家自然科学基金(81503437)
江西省自然科学基金(20181BAB2050)
关键词
原发性肝癌
高通量筛选技术
新型小分子化合物
细胞生长
primary liver cancer
high throughput screening
novel small molecular weight compounds
cellular growth
