title: Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma.
abstract: BACKGROUND
  High expression of telomerase and Bcl-2 are reported in hepatocellular carcinoma. Some anticancer drugs show their effects through reduction of these factors. In this study, it was aimed to investigate the effects of a new synthetic compound, platinum azidothymidine, on inhibition of telomerase and Bcl-2 expression in hepatocellular carcinoma compared to azidothymidine.
  
  
  METHODS
  To study the effects of Pt-AZT on hepatocellular carcinoma and compare its effects with AZT in inhibition of telomerase and Bcl-2 gene expression, pathogen-free male Wistar rats (n=100) were used. They were randomly divided to 4 groups (n=25). Group A as the control group contained 25 healthy rats; in the rest of animals, preneoplastic lesions were induced in their livers (groups B, C, and D) using Solt-Farber resistant hepatocyte protocol. Cancer development was approved by a pathology laboratory. Group B was negative control (untreated), groups C and D were treated by intraperitoneal injection (IP) of Pt-AZT (0.9 mg/kg/day) and AZT (0.3 mg/kg/day), respectively for 14 days. At the end of the protocol, all rats were sacrificed and Bcl-2 and telomerase gene expression was determined using real-time PCR.
  
  
  RESULTS
  No tumor in the livers was found in group A at any point of the study, but it was present in livers of all animals in B, C and D groups. Results showed that telomerase and Bcl-2 expression was significantly lower in group C compared with group B (0.473±0.231 vs. 5.137±5.08, p<0.001, for telomerase expression, and 0.41±0.276 vs. 7.25±11.6, p<0.001, for Bcl-2 expression) and also compared with group D (0.473±0.231 vs. 3.48±4.02, p<0.001, for telomerase expression, and 0.41±0.276 vs. 4.93±18, p<0.001, for Bcl-2 expression).
  
  
  CONCLUSIONS
  For the first time, it was demonstrated that Pt-AZT has more inhibitory effect on telomerase and Bcl-2 expression than AZT. It effectively inhibits the growth of liver tumor in rats by extending apoptosis.
authors.affiliation: Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Sabokrouh
authors.affiliation: Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.affiliation: Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran ; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Goodarzi
authors.affiliation: Department of Clinical Biochemistry, Pasteur Institute, Tehran, Iran.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Khatami
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Massoud
authors.initials: M
authors.lastname: Taghizadeh-Jahed
authors.affiliation: Department of Chemistry, Razi University of Kermanshah, Kermanshah, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Shahabadi
authors.affiliation: Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors.forename: Niknam
authors.initials: N
authors.lastname: Lakpour
authors.affiliation: Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Shakiba
keywords: Gene expression; Hepatocellular carcinoma; Platinum; Telomerase