Interferon-alpha modulates resistance to cisplatin in three human hepatoma cell lines.
We investigated the expression of the drug resistance-related genes, multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase IIalpha, DNA topoisomerase IIbeta, and glutathione-S-transferase pi gene (GST-pi) in three human hepatoma cell lines (HepG 2, HuH 7, SK-Hep-1) with or without drug treatment with interferon-alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymerase chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase IIalpha, and topoisomerase IIbeta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-1, the administration of CDDP alone increased the signals of MDR1 while the addition of IFN-alpha decreased the signals, and the signals of GST-pi were decreased by IFN-alpha plus CDDP. In summary, our results concerning the expression of drug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver cancer.
Takeuchi
A
A
First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Kaneko
S
S
Matsushita
E
E
Urabe
T
T
Shimoda
A
A
Kobayashi
K
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage*; D004264:DNA Topoisomerases, Type I / Q000032:analysis; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019450:Genes, MDR; D018197:Hepatoblastoma / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016898:Interferon-alpha; D004264:DNA Topoisomerases, Type I; D002945:Cisplatin