庄喜兵,陈伟,乔田奎,査琳,袁素娟.含非甲基化二核苷酸的寡脱氧核苷酸1826对Lewis肺癌放疗联合作用及其剂量-效应关系[J].中华放射医学与防护杂志,2012,32(3):266-269
含非甲基化二核苷酸的寡脱氧核苷酸1826对Lewis肺癌放疗联合作用及其剂量-效应关系
Dose response of CpG ODN1826 and its combination effect with X-ray irradiation on Lewis lung cancer in mice
投稿时间:2011-07-08  
DOI:10.3760/cma.j.issn.0254-5098.2012.03.011
中文关键词:  Lewis肺癌  含非甲基化二核苷酸的寡脱氧核苷酸  X射线照射  肿瘤生长延迟  凋亡
英文关键词:Lewis lung cancer  Unmethylated cytosine-phosphate-guanine oligodeoxy-nucleotide, CpG ODN  X-ray irradiation  Tumor growth delay  Apoptosis
基金项目:
作者单位E-mail
庄喜兵 200540 上海, 复旦大学附属金山医院肿瘤科  
陈伟 200540 上海, 复旦大学附属金山医院肿瘤科  
乔田奎 200540 上海, 复旦大学附属金山医院肿瘤科 qiaotk@yahoo.com.cn 
査琳 200540 上海, 复旦大学附属金山医院肿瘤科  
袁素娟 200540 上海, 复旦大学附属金山医院肿瘤科  
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中文摘要:
      目的 探讨含非甲基化二核苷酸的寡脱氧核苷酸(unmethylated cytosine-phosphate-guanine oligodeoxynucleotide, CpG ODN)1826对X射线照射荷瘤小鼠Lewis肺癌的联合作用及其剂量-效应关系。方法 在C57BL/6J纯系小鼠右前腋窝接种Lewis肺癌细胞,制备荷瘤小鼠模型。将64只荷瘤小鼠按完全随机化方法随机分为对照组、 X射线照射(IR)组、低剂量CpG ODN1826组(0.15 mg)、中剂量CpG ODN1826组(0.30 mg)、高剂量CpG ODN1826组(0.45 mg)、低剂量CpG ODN826+ IR组(CpG1826 0.15 mg+IR)、中剂量CpG ODN1826+ IR组(CpG 0.30 mg+IR)和高剂量CpG ODN1826+ IR组(CpG 0.45 mg+IR),每组8只。实验的第1、2、9天注射CpG ODN1826。实验的第2天开始X射线照射,1次/d, 2.50 Gy/次,总剂量12.50 Gy。观察各组移植瘤生长速度和各治疗组肿瘤生长延迟时间(TGD),用DNA断裂的原位末端标记法检测细胞凋亡。结果 成功建立荷瘤小鼠Lewis肺癌模型,成瘤率为100%。经治疗后,各组小鼠肿瘤体积都较对照组明显减小,CpG ODN1826 0.45 mg+IR组移植瘤体积最小。 DNA断裂的原位末端标记法(TUNEL)法检测细胞凋亡率分别为(2.40±0.55)%、(5.50±0.76)%、(7.13±0.83)%、(11.63±1.06)%、(19.13±0.83)%、(12.88±0.83)%、(20.57±2.37)%和(28.17±3.31)%。各治疗组都明显高于对照组(t=11.15、7.91、17.82、39.48、24.73、16.61和17.05,P<0.05﹚,不同剂量CpG ODN1826+IR组显著高于IR组(t=13.78、15.08和17.47,P<0.05﹚和不同剂量CpG ODN1826组(t=18.53、9.66和7.51,P<0.05﹚。结论 CpG ODN1826能明显地抑制肿瘤细胞生长,促进肿瘤细胞凋亡,且呈剂量-效应关系。
英文摘要:
      Objective To explore the combination effect of unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN)1826 and X-rays on Lewis lung cancer in mouse and the dose response of CpG ODN.Methods The tumor-bearing mouse model was established by injecting Lewis lung cancer cells into the right infra-axillary dermis of mouse. Sixty-four C57BL/6 J mice were evenly randomized into eight groups with 8 mice each: control group, IR group, CpG OND1826 0.15 mg group, CpG OND1826 0.3 mg group, CpG OND1826 0.45 mg group, CpG OND1826 0.15 mg+IR group, CpG OND1826 0.30 mg+IR group, and CpG OND1826 0.45 mg+IR group. On the 1st, 2nd, and 9th days, CpG ODN was injected into mouse. After 3 hours of injection, the mice were start to irradiate with X-rays once a day on the 2nd-6th days,and the total dose was 12.50 Gy. Tumor growth and TGD were measured, and the apoptosis of tumor cells were examined with TUNEL.Results The Lewis lung cancer-bearing model was successfully established in all mice. Under the treatments of CpG OND1826 and irradiation, the tumor volumes were smaller than that of control group, and the tumor volumes of CpG OND1826 0.45 mg+IR group was the smallest. TUNEL results revealed that the apoptosis rate were (2.40±0.51)% in control group,(5.62±0.50)% in IR, (7.13±0.83)% in CpG OND1826 0.15 mg, (11.63±1.06)% in CpG OND1826 0.3 mg, (19.13±0.83)% in CpG OND1826 0.45 mg, (12.88±0.83)% in CpG OND1826 0.15 mg+IR, (20.57±2.37)% in CpG OND1826 0.3 mg+IR, and (28.17±3.31)% in CpG OND1826 0.45 mg+IR group, and thus the apoptosis rate of every therapy group was higher than that in control(t=11.15, 7.91, 17.82, 39.48, 24.73, 16.61 and 17.05, P<0.05). The apoptosis rates of CpG ODN1826 plus X-ray irradiation group were significantly higher than those in IR alone(t=13.78, 15.08 and 17.47, P<0.05﹚or CpG ODN group (t=18.53, 9.66 and 7.51,P<0.05).Conclusions CpG ODN1826 can dramatically increase the efficiency of radiotherapy by inhibiting tumor growth and promoting tumor apoptosis.
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