Gene expressions associated with chemosensitivity in human hepatoma cells.
OBJECTIVE
Only limited patients with hepatoma benefit from chemotherapy without a clear explanation. We aimed to identify genes associated with chemosensitivity using transcriptional profiles.


METHODS
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.
Hoshida
Yujin
Y
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Moriyama
Masaru
M
Otsuka
Motoyuki
M
Kato
Naoya
N
Taniguchi
Hiroyoshi
H
Shiratori
Yasushi
Y
Seki
Naohiko
N
Omata
Masao
M
D000951:Antigens, Neoplasm / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D026901:Membrane Transport Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C043912:peptide permease; D013482:Superoxide Dismutase; D004250:DNA Topoisomerases, Type II