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