Azidothymidine inhibits cell growth and telomerase activity and induces DNA damage in human esophageal cancer.
Mol Med Rep
; 15(6): 4055-4060, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28487971
ABSTRACT
Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE11. A telomeric repeat amplification assay was utilized to detect telomerase activity following treatment of TE11 cells with AZT. The effect of AZT on TE11 cell cycle distribution was determined by flow cytometry. Cellular DNA damage was evaluated by a comet assay and an MTT assay demonstrated that AZT significantly inhibited the viability of TE11 cells, in a timeand dosedependent manner. In addition, TE11 cells treated with various concentrations of AZT exhibited a significant reduction in telomerase activity and percentage of cells in the G1/G0 phase, and an increase in the percentage of cells in the S phase. High doses of AZT caused DNA damage, and enhanced the expression levels of γH2A histone family member X and phosphorylated checkpoint kinase 2 in TE11 cells. These results demonstrated that AZT effectively inhibits proliferation of the TE11 human esophageal cancer cell line in vitro. The growth inhibitory effects were associated with a reduction in telomerase activity, S and G2/M phase cell cycle arrest, and enhanced DNA damage, suggesting that AZT may be utilized in the clinic for the treatment of esophageal cancer.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
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Esofago
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Neoplasias Esofágicas
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Zidovudina
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Telomerase
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2017
Tipo de documento:
Article