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

Antisense oligodeoxynucleotides targeting ATM strengthen apoptosis of laryngeal squamous cell carcinoma grown in nude mice.
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靶向ATM的反义寡脱氧核苷酸增强裸鼠喉鳞状细胞癌的凋亡

DOI:
10.1186/1756-9966-30-43
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发表时间:
2011-04-17
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Liu S
Liu S
中科院分区:
其他
文献类型:
--
作者:
Feng J;Zou J;Li L;Zhao Y;Liu S

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背景为了保护喉鳞状细胞癌(LSCC)患者的喉功能,提高其生活质量,我们设计了反义寡脱氧核苷酸(AS-ODN)来降低ATM的表达,并增强hep-2(人表皮样喉癌)细胞体内外辐射的凋亡。方法分别采用实时定量PCR和Western blotting检测hep-2细胞中ATM mRNA和蛋白的表达。采用克隆存活实验检测照射后hep-2细胞的存活能力,并通过流式细胞仪分析细胞凋亡情况。测量实体瘤体积,TUNEL法和Western blotting分析照射后细胞凋亡和蛋白表达。结果ATM AS-ODNs处理后的hep-2细胞中ATM mRNA和蛋白相对表达量分别降低至未处理细胞的11.03±2.51%和48.14±5.53%(P <0.05)。照射后,相同照射剂量下,ATM AS-ODNs处理的细胞存活分数(SF)低于其他组(P < 0.05)。单独接受X射线照射的hep-2细胞实体瘤的抑制率为5.95±4.52%,而联合ATM AS-ODNs治疗组的抑制率为34.28±2.43%(P < 0.05)。联合ATM AS-ODNs注射照射组细胞凋亡指数为17.12±4.2%,显着高于其他组(P < 0.05)。结论ATM AS-ODNs在体外和体内均可降低ATM表达,增强hep-2细胞对辐射的凋亡。
BackgroundTo 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.MethodsThe 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.ResultsThe 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).ConclusionAS-ODNs of ATM reduce ATM expression and enhance hep-2 cells apoptosis to radiation in vitro and in vivo.
DOI: 10.1038/nature03482
发表时间: 2005-04-14
期刊: NATURE
影响因子: 64.8
作者:
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者: Bartek, J
DOI: 10.1523/jneurosci.21-17-06687.2001
发表时间: 2001-09-01
影响因子: 5.3
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通讯作者: McKinnon, PJ
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发表时间: 2001-01-01
影响因子: 2.8
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影响因子: --
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Sakata, Koh-Ichi;Someya, Masanori;Hareyama, Masato
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DOI: 10.1074/jbc.m410873200
发表时间: 2005-01-14
影响因子: 4.8
作者:
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通讯作者: O'Reilly, MA