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Series GSE12307 Query DataSets for GSE12307
Status Public on Dec 31, 2008
Title siRNA Administration Against AFP Inhibits Hepatocellular Carcinoma Proliferation in Vitro and Progression in Mice
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Increased α-fetoprotein (AFP) levels have been reported to predict a poor prognosis in hepatocellular carcinoma (HCC). We assessed the mechanism of AFP involvement in the progression of HCC and determined whether AFP could be a molecular target. We used human HCC cell lines to assess proliferation and apoptosis response to exogenous AFP. We introduced AFP small interfering RNA (siRNA) into HCC cell lines to examine whether it could inhibit cell proliferation and anti-apoptotic properties. The effects of systemically introduced AFP siRNA were assessed using a tumor xenotransplantation model. The effects of AFP on gene expression in HCC cell lines and human HCC specimens were examined. Exogenous AFP induced cell proliferation dose-dependently and inhibited apoptosis induced by 5-fluorouracil (5-FU) in all cell lines examined. AFP siRNA inhibited the proliferation of AFP-producing HCC cell lines and induced apoptosis in co-cultures with 5-FU. Tumor sizes in mice treated with AFP siRNA were significantly smaller than those in controls. AFP siRNA administration in mice induced a low proliferation index and a high apoptosis index in tumors. cDNA microarray analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot using HepG2 and HLE cells with AFP showed that AFP reduced expression of genes related to apoptosis (DFFB) and tumor suppression (NDRG2). Expression of these molecules was also suppressed in human HCC tissues that overexpress AFP. AFP is not only a passive tumor marker, but also an active tumor stimulator through several mechanisms. AFP siRNA introduction may be of possible therapeutic use for HCC.

Keywords: Genetic modification
Overall design Two-condition experiment, Control vs. AFP-stimulated cells.
Contributor(s) Mitsuhashi N, Miyazaki M
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Submission date Jul 31, 2008
Last update date Feb 22, 2018
Contact name Noboru Mitsuhashi
Phone +81-43-290-3124
Organization name Research Center for Frontier Medical Engineering, Chiba University
Department Section for Medical Nanotechniques
Street address 1-33 Yayoi-cho, Inage-ku
City Chiba
ZIP/Postal code 263-8522
Country Japan
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (2)
GSM309469 HepG2 cells stimulated with AFP
GSM309470 HLE cells stimulated with AFP
BioProject PRJNA113613

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Supplementary file Size Download File type/resource
GSE12307_RAW.tar 34.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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