PMID- 21496344 OWN - NLM STAT- MEDLINE DCOM- 20111103 LR - 20211203 IS - 1756-9966 (Electronic) IS - 0392-9078 (Print) IS - 0392-9078 (Linking) VI - 30 IP - 1 DP - 2011 Apr 17 TI - Antisense oligodeoxynucleotides targeting ATM strengthen apoptosis of laryngeal squamous cell carcinoma grown in nude mice. PG - 43 LID - 10.1186/1756-9966-30-43 [doi] AB - 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. FAU - Feng, Jun AU - Feng J AD - Department of Otolaryngology-Head and Neck Surgery, West China hospital of Sichuan University, Chengdu, PR China. FAU - Zou, Jian AU - Zou J FAU - Li, Li AU - Li L FAU - Zhao, Yongsheng AU - Zhao Y FAU - Liu, Shixi AU - Liu S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110417 PL - England TA - J Exp Clin Cancer Res JT - Journal of experimental & clinical cancer research : CR JID - 8308647 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Oligonucleotides, Antisense) RN - 0 (RNA, Messenger) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.11.1 (ATM protein, human) RN - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins) RN - EC 2.7.11.1 (Atm protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Animals MH - *Apoptosis MH - Ataxia Telangiectasia Mutated Proteins MH - Carcinoma, Squamous Cell/genetics/pathology/*therapy MH - Cell Cycle Proteins/*antagonists & inhibitors/genetics MH - Cell Line, Tumor MH - DNA-Binding Proteins/*antagonists & inhibitors/genetics MH - Flow Cytometry MH - Genetic Therapy MH - Laryngeal Neoplasms/genetics/pathology/*therapy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - *Oligonucleotides, Antisense MH - Protein Serine-Threonine Kinases/*antagonists & inhibitors/genetics MH - RNA, Messenger/metabolism MH - Transfection MH - Tumor Suppressor Proteins/*antagonists & inhibitors/genetics PMC - PMC3097000 EDAT- 2011/04/19 06:00 MHDA- 2011/11/04 06:00 PMCR- 2011/04/17 CRDT- 2011/04/19 06:00 PHST- 2010/12/27 00:00 [received] PHST- 2011/04/17 00:00 [accepted] PHST- 2011/04/19 06:00 [entrez] PHST- 2011/04/19 06:00 [pubmed] PHST- 2011/11/04 06:00 [medline] PHST- 2011/04/17 00:00 [pmc-release] AID - 1756-9966-30-43 [pii] AID - 10.1186/1756-9966-30-43 [doi] PST - epublish SO - J Exp Clin Cancer Res. 2011 Apr 17;30(1):43. doi: 10.1186/1756-9966-30-43.