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免疫病理疾病及治疗学论文学
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN 打印: 2151-8017
ISSN 在线: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

免疫病理疾病及治疗学论文学

DOI: 10.1615/ForumImmunDisTher.v2.i2.40
pages 127-135

Induction of Apoptosis and Chemosensitization by the Histone Deacetylase Inhibitor Trichostatin in Hepatocellular Carcinoma Cells: Molecular Analysis and RKIP Levels

Luigi Inguglia
Department STEBICEF, University of Palermo, Palermo, Italy; Euro Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
Monica Notarbartolo
Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro", University of Palermo; Palermo, Italy
Paola Poma
Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro", University of Palermo; Palermo, Italy
Manuela Labbozzetta
Pharmacology Unit, Department of Health Sciences and Mother and Child Care "G. D'Alessandro", University of Palermo; Palermo, Italy
Natale D'Alessandro
Pharmacology Unit, University of Palermo Department of Health Sciences and Mother and Child Care "Giuseppe D'Alessandro" Palermo, Italy

ABSTRACT

The mRNA and protein levels of RKIP are reduced and those of YY1 increased in clinical HCC. Loss, mutation, or promoter hypermethylation of the RKIP gene may not account for the downregulation of RKIP in HCC. Histone deacetylation can silence gene expression and play a significant role in hepatocarcinogenesis. The histone deacetylase inhibitor (HDACI) trichostatin induced cell growth inhibition and proapoptotic effects in HA22T/VGH and HepG2 HCC cells; it also exhibited synergy with doxorubicin. Treatment with trichostatin caused histone hyperacetylation and down- or upregulated expression of different genes (such as β-catenin, cyclin D1, hTERT, XIAP, and IL-6). These changes might, at least in part, explain the anticancer and chemosensitizing activities of trichostatin. Nevertheless, trichostatin did not modify RKIP or YY1 mRNA and protein levels in the two representative HCC cell lines. Although further studies are necessary to clarify the possible role of epigenetic changes in the expression of RKIP and YY1, our results underline the therapeutic potential of HDACIs in HCC.