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Hepatogastroenterology. 2007 Mar;54(74):489-92.

Gene expressions associated with chemosensitivity in human hepatoma cells.

Author information

1
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Abstract

BACKGROUND/AIMS:

Only limited patients with hepatoma benefit from chemotherapy without a clear explanation. We aimed to identify genes associated with chemosensitivity using transcriptional profiles.

METHODOLOGY:

In 8 hepatoma cells (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2) transcriptional profiles were obtained using cDNA microarray including 2300 genes. Chemosensitivities to 8 anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) were measured by obtaining 50% growth inhibitory concentrations (GI50) using MTT assay. Genes having drug-specific association with chemosensitivity were selected.

RESULTS:

Up-regulation of topoisomerase II beta was associated with chemo-resistance, the target of doxorubicin. Platinum-specific resistance was associated with superoxide dismutase 2 expression. Antigen peptide transporter 1 expression correlated with nimustine and mitoxantrone-specific susceptibility. These results were verified by semi-quantitative RT-PCR. Drug inactivators reported in non-liver cancers such as multidrug transporters and drug metabolizers showed less diversity of chemosensitivity in hepatoma cells.

CONCLUSIONS:

To evaluate these gene expressions may be useful to select anticancer drugs, and possibly to consider new therapeutic target to modify drug action.

PMID:
17523305
[Indexed for MEDLINE]

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