Interferon-alpha modulates resistance to cisplatin in three human hepatomacell lines

We investigated the expression of the drug resistance-related genes, multid rug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), and the DNA topoisomerase II alpha, DNA topoisomerase II beta, and g lutathione-S-transferase pi gene (GST-lr) in three human hepatoma cell line s (HepG 2, HuH 7, SK-Hep-l) with or without drug treatment with interferon- alpha (IFN-alpha) and cisplatin (CDDP), by a reverse transcription-polymera se chain reaction (RT-PCR) method and a competitive PCR method. The signals of the MDR1, MRP, topoisomerase II alpha, and topoisomerase II beta genes in HepG2 were weakened when IFN-alpha was added to CDDP. In SK-Hep-l, the a dministration of CDDP alone increased the signals of MDR1 while the additio n of IFN-a decreased the signals, and the signals of GST-pi were decreased by IFN-a plus CDDP, In summary, our results concerning the expression of dr ug resistance-related genes in three human hepatoma cell lines demonstrate that IFN-alpha may modulate the mechanism of resistance to CDDP in liver ca ncer.