Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth.
Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth.
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连续低能量 125I 种子照射改变 DNA 甲基转移酶表达模式并抑制胰腺癌肿瘤生长
DOI：
10.1186/1756-9966-30-35
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发表时间：
2011-04-02
期刊：
影响因子：
--
通讯作者：
Zhao-shen L
中科院分区：
文献类型：
--
作者：
Ma JX;Jin ZD;Si PR;Liu Y;Lu Z;Wu HY;Pan X;Wang LW;Gong YF;Gao J;Zhao-shen L
碘125(125I)粒子照射是治疗不能切除的胰腺癌的有效方法。然而，近距离放射治疗的放射生物学机制仍不清楚。因此，我们研究了持续和低能量125I照射对胰腺癌细胞凋亡、DNA甲基转移酶(DNMT)表达和细胞生长的影响。材料与方法采用125I粒子体外照射，将SW-1990细胞分为3组：对照组(0GY)、2Gy组和4Gy组。为了建立胰腺癌的动物模型，通过外科手术将SW1990细胞植入小鼠胰腺。移植后10d，30只胰腺癌小鼠接受125I粒子植入，随机分为3组：0Gy2Gy4Gy组。照射后48h和72h，流式细胞仪检测细胞凋亡，实时荧光定量聚合酶链式反应和蛋白印迹分析检测Dnmts基因和蛋白表达的变化。125I粒子植入28d后，采用原位末端标记法检测细胞凋亡，免疫组织化学方法检测DNMTS蛋白的表达。结果125I粒子照射可诱导肿瘤细胞发生明显的细胞凋亡，以4Gy时最为明显。2Gy组DNMT1和DNMT3b的mRNA和蛋白表达均显著高于对照组。相反，4Gy细胞组Dnmt3b基因和蛋白的表达明显低于对照组。125I粒子植入治疗组的TUNEL阳性细胞数明显多于对照组，尤其是在4Gy时。4Gy粒子植入组DNMT1和Dnmt3b蛋白染色较对照组弱。结论125I粒子植入对胰腺癌细胞有明显的杀伤作用，尤其是在4Gy时，125I诱导的细胞凋亡和DNMT1、Dnmt3b表达的变化为近距离放射治疗提供了潜在的机制。
BackgroundIodine 125 (125I) seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the influence of continuous and low-energy125I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.Materials and methodsForin vitro125I seed irradiation, SW-1990 cells were divided into three groups: control (0 Gy), 2 Gy, and 4 Gy. To create an animal model of pancreatic cancer, the SW 1990 cells were surgically implanted into the mouse pancreas. At 10 d post-implantation, the 30 mice with pancreatic cancer underwent125I seed implantation and were separated into three groups: 0 Gy, 2 Gy, and 4 Gy group. At 48 or 72 h after irradiation, apoptosis was detected by flow cytometry; changes in DNMTs mRNA and protein expression were assessed by real-time PCR and western blotting analysis, respectively. At 28 d after125I seed implantation,in vivoapoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after125I seed implantation.Results125I seed irradiation induced significant apoptosis, especially at 4 Gy. DNMT1 and DNMT3b mRNA and protein expression were substantially higher in the 2 Gy group than in the control group. Conversely, the 4 Gy cell group exhibited significantly decreased DNMT3b mRNA and protein expression relative to the control group. There were substantially more TUNEL positive in the125I seed implantation treatment group than in the control group, especially at 4 Gy. The 4 Gy seed implantation group showed weaker staining for DNMT1 and DNMT3b protein relative to the control group. Consequently,125I seed implantation inhibited cancer growth and reduced cancer volume.Conclusion125I seed implantation kills pancreatic cancer cells, especially at 4 Gy.125I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.
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DOI：
10.1016/j.ijrobp.2004.12.074
发表时间：
2005-08-01
影响因子：
7
作者：
Cohen, SJ;Dobelbower, R;Haller, DG
通讯作者：
Haller, DG
影响因子：
3.9
作者：
Kim, Sung Youl;Yang, Eun Sun;Park, Jeen-Woo
通讯作者：
Park, Jeen-Woo
影响因子：
5.1
作者：
Batra, Vipen;Sridhar, Swathi;Devasagayam, Thomas Paul Asir
通讯作者：
Devasagayam, Thomas Paul Asir
影响因子：
11.2
作者：
Glover, Louise E.;Newton, Kimberly;Krishnan, Gomathi;Bronson, Roderick;Boyle, Alexandra;Krivickas, Lisa S.;Brown, Robert H., Jr.
通讯作者：
Brown, Robert H., Jr.
影响因子：
11.2
作者：
Harrington, Emily P.;Zhao, Chao;Fancy, Stephen P. J.;Kaing, Sovann;Franklin, Robin J. M.;Rowitch, David H.
通讯作者：
Rowitch, David H.