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

作　　者：庄喜兵[1] 陈伟[1] 乔田奎[1] 查琳[1] 袁素娟[1] 

机构地区：[1]复旦大学附属金山医院肿瘤科,上海200540

出　　处：《中华放射医学与防护杂志》2012年第3期266-269,共4页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的探讨含非甲基化二核苷酸的寡脱氧核苷酸（unmethylatedcytosinephosphate-guanine oligodeoxynucleotide，CpGODN）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CpGODN1826组（0．15mg）、中剂量CpGODN1826组（0．30mg）、高剂量CpGODN1826组（0．45mg）、低剂量CpG0DN826＋IR组（CpG18260．15mg＋IR）、中剂量CpGODN1826＋IR组（CpG0．30mg＋IR）和高剂量CpG0DN1826＋IR组（CpG0．45mg＋IR），每组8只。实验的第1、2、9天注射CpGODN1826。实验的第2天开始x射线照射，1次／d，2．50Gy／次，总剂量12．50Gy。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，CpGODN18260．45mg＋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CpGODN1826＋IR组显著高于IR组（t=13．78、15．08和17．47，P〈0．05）和不同剂量CpGODN1826组（t=18．53、9．66和7．51，P〈0．05）。结论CpGODN1826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。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 0ND1826 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 0ND1826 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 OND18260.15 mg, （11.63 ±1.06）% in CpG 0ND18260.3 mg, （19.13±0.83）% in CpG OND18260.45 mg, （12.88 ＋0.83）% in CpG OND18260.15 mg＋ IR, （20.57 ±2.37）% in CpG 0ND1826 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 apoptosisrates 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 ） orCpGODN group （t=18.53, 9.66 and7.51, P〈0.05）. Conclusions CpG 0DN1826 can dramatically increase the efficiency o

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 

分 类 号：R734.2[医药卫生—肿瘤]