Modulating IGFBP-3 expression by trichostatin A: Potential therapeutic role in the treatment of hepatocellular carcinoma

The Hep3B cell line analyzed in the present study is a widely used in vitro model in studies characterizing pathogenetic, functional, and therapeutic aspects of human hepatocellular carcinoma (HCC). Here we have determined th e chromosomal composition using a combination of cytogenetic techniques. In agreement with the original description for this cell line, Hep3B was foun d to have a hypotriploid chromosome content carrying 59-63 chromosomes and no cytogenetic differences were demonstrated between early and late passage s suggesting that this cell line has remained stable after repeated subcult uring. Mutations and alterations of the IGF-axis as well as of chromosome 1 p34, where the genes for histone deacetylase 1 (HDAC1) and transforming gro wth factor beta receptor interacting protein-1 (TRIP-1) map, are frequent e vents in hepatocarcinogenesis. This study characterizes the Hep3B cell line in detail at the karyotypic level, using comparative genomic hybridization (CGH), spectral karyotyping (SKY), G-banding and FISH techniques. We have also examined the effects of the histone deacetylase inhibitor trichostatin A (TSA) on members of the IGF-axis, and analysed them with regard to the k aryotype. The results show that expression of one member of the IGF-axis, I GFBP-3, is greatly upregulated by treatment of Hep3B cells with TSA. As IGF BP-3 has been shown to induce apoptosis, these results suggest a possible u se for histone deacetylase inhibitors and/or IGFBP-3 in the treatment of HC C.