title: Antisense oligonucleotides directed against insulin-like growth factor-II messenger ribonucleic acids delay the progress of rat hepatocarcinogenesis.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a multistep complex process, caused by many of genetic alteration. Insulin-like growth factors and their receptor have been widely implicated to HCC. Insulin-like growth factor-II (IGF-II) is a mitogenic polypeptide, found in various fetal and neonatal tissues of humans and rats and expresses in HCC. Here we investigated anticancer potential of phosphorothioate antisense oligonucleotides (ASOs) against three coding exons (exon-1/exon-2/exon-3) of IGF-II messenger ribonucleic acid in rat hepatocarcinogenesis model.
  
  
  METHODS
  During diethylnitrosamine and 2-acetylaminofluorene induced hepatocarcinogenesis, rats were treated with ASOs. Various biochemical and histological studies were conducted.
  
  
  RESULTS
  About 40% of carcinogen treated rats, which received two oligomers (against exon-1 or-3) did not show any hepatic lesion, hyperplastic nodule or tumor and remaining 60% of those rats showed lesion incidence and had about 59% and 55% reductions in the numbers of hepatic altered foci, respectively. Reductions in the total lesion-area when compared with carcinogen control rats were 64% and 53%, respectively for the animals treated with carcinogen and received the ASOs against exon-1/-3. Fluorescein isothiocyanate-labeled ASO reached in the hepatocytes in 2 h. No predominant IGF-II overexpression was observed in case of rats treated with the two ASOs. Treatment of the antisense IGF-II oligomers in carcinogen treated rats show better hepatocellular integrity along with several preneoplastic/neoplastic marker isoenzyme/enzyme modulations.
  
  
  CONCLUSIONS
  Two of the three antisense oligomer-types effectively controlled IGF-II overexpression, causing the delay of the development and/or progress of hepatic cancer in rats.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India ; Georg-August-Universität Göttingen, Department of Human Genetics, Heinrich-Düker Weg 12, 37073 Göttingen, Germany.
authors.forename: Miltu Kumar
authors.initials: MK
authors.lastname: Ghosh
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Falguni
authors.initials: F
authors.lastname: Patra
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Shampa
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Chowdhury Mobaswar
authors.initials: CM
authors.lastname: Hossain
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Mukherjee
keywords: Antisense oligonucleotides; hepatic altered foci; hepatocellular carcinoma; hyperplastic nodules; insulin-like growth factor
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