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

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.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).AS-ODNs of ATM reduce ATM expression and enhance hep-2 cells apoptosis to radiation in vitro and in vivo.With advanced technique development in treatments of LSCC, radiotherapy is superior in its ability to conserve function in the treatment of initial laryngeal squamous cell carcinoma (LSCC). However, because of laryngeal cancer radiation resistance, which result in the low effectiveness and high recurrence when treated with radiotherapy alone [1,2]. So it is important significance to improve the LSCC radiosensitivity. Hep-2 cells, or laryngeal squamous cell carcinoma cell lines, are helpful in studying the biological behavior of LSCC. In the latest study, Hep-2 cells were found to be resistant to radiotherapy [3]. Ataxia-telangiectasia (A-T) is characterized by impaired recognition and repair of DNA damage and increased sensit