Author/Authors :
Sabokrouh, Abdolreza Department of Clinical Biochemistry - Hamadan University of Medical Sciences , Vaisi-Raygani, Asad Molecular Diagnostic Research Center - Kermanshah University of Medical Sciences , Goodarzi, Mohammad Taghi Research Center for Molecular Medicine - Hamadan University of Medical Sciences , Khatami, Shohreh Department of Clinical Biochemistry - Pasteur Institute , Taghizadeh-jahed, Massoud Reproductive Biotechnology Research Center - Avicenna Research Institute , Shahabadi, Nahid Department of Chemistry - Razi University of Kermanshah , Lakpour, Niknam Reproductive Biotechnology Research Center - Avicenna Research Institute , Shakiba, Yadollah Molecular Diagnostic Research Center - Kermanshah University of Medical Sciences
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).
Conclusion: 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.
Keywords :
Telomerase , Platinum , Hepatocellular carcinoma , Gene expression
