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Series GSE77322 Query DataSets for GSE77322
Status Public on Mar 01, 2017
Title Niclosamide ethanolamine reverses gene expression and inhibits growth of hepatocellular carcinoma in vitro and in vivo
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Hepatocellular carcinoma (HCC) is a fatal malignancy with a dismal prognosis. The recent advances in genomics and transcriptomics have led to large volumes of molecular data for HCC, providing an unprecedented opportunity to translate these data into more effective therapeutics. By creating HCC gene expression signatures and comparing with drug response signatures from multiple datasets, we identified four antihelminthics (from over 1000 FDA-approved drugs) that can reverse the HCC disease gene expression. Among these four, niclosamide was the top hit, which we further evaluated in clinically relevant HCC cell lines and patient-derived xenografts (PDX). Given the poor water-solubility and limited systemic bioavailability of niclosamide, we also evaluated its ethanolamine salt (NEN), which has improved solubility and bioavailability. Both niclosamide and NEN significantly inhibited HCC cell proliferation in vitro, which was associated with down-regulation of key proteins involved in the AKT-mTOR, Wnt, Stat3, and EGFR/Ras/Raf signaling pathways. NEN additionally decreased the growth of three PDX models after oral administration (1,5000 ppm in food) for 4-6 weeks. Expression profiling demonstrated that niclosamide and NEN induced highly similar gene expression changes in HepG2 cells and in PDX models, and that both compounds significantly reversed HCC gene expression in vitro and in vivo . Our results suggest that NEN may be a preferred drug candidate for the treatment of HCC.
 
Overall design Total RNA obtained from HepG2 cells after treatment with vehicle, NEN, and niclosamide for 6 hours, and from tumors after treatment with NEN and control for 6 weeks
 
Contributor(s) Chen B, Wei W, Li M, Chua M, Butte AJ, So S
Citation(s) 28284560
Submission date Jan 27, 2016
Last update date Aug 13, 2018
Contact name Bin Chen
E-mail(s) bin.chen@ucsf.edu
Organization name UCSF
Street address 550 16th Street, 4th Floor
City San Francisco
State/province California
ZIP/Postal code 94143
Country USA
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (9)
GSM2049228 HepG2
GSM2049229 HepG2 + NEN
GSM2049230 HepG2 + Niclosamide
Relations
BioProject PRJNA310069

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77322_RAW.tar 26.2 Mb (http)(custom) TAR
GSE77322_non-normalized_data.txt.gz 2.7 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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