Antisense oligodeoxynucleotides targeting ATM strengthen apoptosis of laryngeal squamous cell carcinoma grown in nude mice

Journal of Experimental & Clinical Cancer Research

Shixi Liu⁴  Yongsheng Zhao²  Li Li³  Jian Zou⁴  Jun Feng¹ 

[1] Sichuan University and working in the Affiliated Hospital of North Sichuan Medical College;Department of cardiothoracia Surgery, West China hospital of Sichuan University, Chengdu, PR China 610041;Department of pathobiology, North Sichuan Medical College, Nanchong, PR China 637000;From the Department of Otolaryngology-Head and Neck Surgery, West China hospital of Sichuan University, Chengdu, PR China 610041

关键词: squamous cell carcinoma;    apoptosis;    Antisense oligodeoxynucleotides;    ATM;   

Others  :  827580
DOI  :  10.1186/1756-9966-30-43

 received in 2010-12-27, accepted in 2011-04-17,  发布年份 2011

【 摘 要 】

Background

To conserve laryngeal function and elevate living quality of laryngeal squamous cell carcinoma (LSCC) patients, we designed antisense oligodeoxynucleotides (AS-ODNs) to reduce expression of ATM and to enhance the apoptosis of hep-2 (Human epidermoid laryngeal carcinoma) cells to radiation in vitro and in vivo.

Methods

The expression of ATM mRNA and protein in hep-2 cells were examined by real-time quantitative PCR and western blotting respectively. Clonogenic survival assay was carried out to detect the survival ability of hep-2 cells after irradiation, and analyzed the cell apoptosis by flow cytometry. The volume of solid tumors was measured, while TUNEL assay and western blotting used to analyze cell apoptosis and protein expression after irradiation.

Results

The relative ATM mRNA and protein expression in hep-2 cells treated with ATM AS-ODNs were decreased to 11.03 ± 2.51% and 48.14 ± 5.53% of that in untreated cells respectively (P <0.05). After irradiation, the survival fraction (SF) of cells treated with ATM AS-ODNs was lower than that of other groups at the same dose of radiation (P < 0.05). The inhibition rate in hep-2 cells solid tumor exposed to X-ray alone was 5.95 ± 4.52%, while it was 34.28 ± 2.43% in the group which irradiated in combination with the treatment of ATM AS-ODNs (P < 0.05). The apoptotic index for the group irradiated in combination with ATM AS-ODNs injection was 17.12 ± 4.2%, which was significantly higher than that of others (P < 0.05).

Conclusion

AS-ODNs of ATM reduce ATM expression and enhance hep-2 cells apoptosis to radiation in vitro and in vivo.

【 授权许可】

   
2011 Feng et al; licensee BioMed Central Ltd.

【 图 表 】

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