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Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma

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 tel...

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Autores principales: Sabokrouh, Abdolreza, Vaisi-Raygani, Asad, Goodarzi, Mohammad Taghi, Khatami, Shohreh, Taghizadeh-jahed, Massoud, Shahabadi, Nahid, Lakpour, Niknam, Shakiba, Yadollah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Avicenna Research Institute 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483314/
https://www.ncbi.nlm.nih.gov/pubmed/26140181
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author Sabokrouh, Abdolreza
Vaisi-Raygani, Asad
Goodarzi, Mohammad Taghi
Khatami, Shohreh
Taghizadeh-jahed, Massoud
Shahabadi, Nahid
Lakpour, Niknam
Shakiba, Yadollah
author_facet Sabokrouh, Abdolreza
Vaisi-Raygani, Asad
Goodarzi, Mohammad Taghi
Khatami, Shohreh
Taghizadeh-jahed, Massoud
Shahabadi, Nahid
Lakpour, Niknam
Shakiba, Yadollah
author_sort Sabokrouh, Abdolreza
collection PubMed
description 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.
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spelling pubmed-44833142015-07-02 Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma Sabokrouh, Abdolreza Vaisi-Raygani, Asad Goodarzi, Mohammad Taghi Khatami, Shohreh Taghizadeh-jahed, Massoud Shahabadi, Nahid Lakpour, Niknam Shakiba, Yadollah Avicenna J Med Biotechnol Original Article 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. Avicenna Research Institute 2015 2015-04 /pmc/articles/PMC4483314/ /pubmed/26140181 Text en Copyright© 2015 Avicenna Research Institute This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.
spellingShingle Original Article
Sabokrouh, Abdolreza
Vaisi-Raygani, Asad
Goodarzi, Mohammad Taghi
Khatami, Shohreh
Taghizadeh-jahed, Massoud
Shahabadi, Nahid
Lakpour, Niknam
Shakiba, Yadollah
Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title_full Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title_fullStr Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title_full_unstemmed Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title_short Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
title_sort comparison between platinum-azidothymidine and azidothymidine effects on bcl-2 and telomerase gene expression in rats with hepatocellular carcinoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483314/
https://www.ncbi.nlm.nih.gov/pubmed/26140181
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