Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth
<p>Abstract</p> <p>Background</p> <p>Iodine 125 (<sup>125</sup>I) seed irradiation is an effective treatment for unresectable pancreatic cancers. However, the radiobiological mechanisms underlying brachytherapy remain unclear. Therefore, we investigated the...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://www.jeccr.com/content/30/1/35 |
| _version_ | 1818664596877082624 |
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| author | Gong Yan-fang Wang Luo-wei Pan Xue Wu Hong-yu Lu Zheng Liu Yan Si Pei-ren Jin Zhen-dong Ma Jian-xia Gao Jun Zhao-shen Li |
| author_facet | Gong Yan-fang Wang Luo-wei Pan Xue Wu Hong-yu Lu Zheng Liu Yan Si Pei-ren Jin Zhen-dong Ma Jian-xia Gao Jun Zhao-shen Li |
| author_sort | Gong Yan-fang |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Iodine 125 (<sup>125</sup>I) 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-energy <sup>125</sup>I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.</p> <p>Materials and methods</p> <p>For <it>in vitro </it><sup>125</sup>I 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 underwent <sup>125</sup>I 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 after <sup>125</sup>I seed implantation, <it>in vivo </it>apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after <sup>125</sup>I seed implantation.</p> <p>Results</p> <p><sup>125</sup>I 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 the <sup>125</sup>I 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, <sup>125</sup>I seed implantation inhibited cancer growth and reduced cancer volume.</p> <p>Conclusion</p> <p><sup>125</sup>I seed implantation kills pancreatic cancer cells, especially at 4 Gy. <sup>125</sup>I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.</p> |
| first_indexed | 2024-12-17T05:35:16Z |
| format | Article |
| id | doaj.art-24ac9513f1a74f8689fd96d15adf3554 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-17T05:35:16Z |
| publishDate | 2011-04-01 |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-24ac9513f1a74f8689fd96d15adf35542022-12-21T22:01:38ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662011-04-013013510.1186/1756-9966-30-35Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growthGong Yan-fangWang Luo-weiPan XueWu Hong-yuLu ZhengLiu YanSi Pei-renJin Zhen-dongMa Jian-xiaGao JunZhao-shen Li<p>Abstract</p> <p>Background</p> <p>Iodine 125 (<sup>125</sup>I) 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-energy <sup>125</sup>I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.</p> <p>Materials and methods</p> <p>For <it>in vitro </it><sup>125</sup>I 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 underwent <sup>125</sup>I 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 after <sup>125</sup>I seed implantation, <it>in vivo </it>apoptosis was evaluated with TUNEL staining, while DNMTs protein expression was detected with immunohistochemical staining. The tumor volume was measured 0 and 28 d after <sup>125</sup>I seed implantation.</p> <p>Results</p> <p><sup>125</sup>I 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 the <sup>125</sup>I 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, <sup>125</sup>I seed implantation inhibited cancer growth and reduced cancer volume.</p> <p>Conclusion</p> <p><sup>125</sup>I seed implantation kills pancreatic cancer cells, especially at 4 Gy. <sup>125</sup>I-induced apoptosis and changes in DNMT1 and DNMT3b expression suggest potential mechanisms underlying effective brachytherapy.</p>http://www.jeccr.com/content/30/1/35<sup>125</sup>I Seed IrradiationPancreatic CancerDNA methyltransferasesDNA hypomethylationApoptosis |
| spellingShingle | Gong Yan-fang Wang Luo-wei Pan Xue Wu Hong-yu Lu Zheng Liu Yan Si Pei-ren Jin Zhen-dong Ma Jian-xia Gao Jun Zhao-shen Li Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth Journal of Experimental & Clinical Cancer Research <sup>125</sup>I Seed Irradiation Pancreatic Cancer DNA methyltransferases DNA hypomethylation Apoptosis |
| title | Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| title_full | Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| title_fullStr | Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| title_full_unstemmed | Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| title_short | Continuous and low-energy <sup>125</sup>I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| title_sort | continuous and low energy sup 125 sup i seed irradiation changes dna methyltransferases expression patterns and inhibits pancreatic cancer tumor growth |
| topic | <sup>125</sup>I Seed Irradiation Pancreatic Cancer DNA methyltransferases DNA hypomethylation Apoptosis |
| url | http://www.jeccr.com/content/30/1/35 |
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