Continuous and low-energy 125I seed irradiation changes DNA methyltransferases expression patterns and inhibits pancreatic cancer tumor growth

Journal of Experimental & Clinical Cancer Research

Li Zhao-shen¹  Jun Gao¹  Yan-fang Gong¹  Luo-wei Wang¹  Xue Pan¹  Hong-yu Wu¹  Zheng Lu¹  Yan Liu¹  Pei-ren Si¹  Zhen-dong Jin¹  Jian-xia Ma¹ 

[1] Department of Gastroenterology, The Changhai Hospital, The Second Military Medical University, Shanghai, PR China

关键词: Apoptosis;    DNA hypomethylation;    DNA methyltransferases;    Pancreatic Cancer;    ¹²⁵I Seed Irradiation;   

Others  :  827616
DOI  :  10.1186/1756-9966-30-35

 received in 2011-01-12, accepted in 2011-04-02,  发布年份 2011

【 摘 要 】

Background

Iodine 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-energy ¹²⁵I irradiation on apoptosis, expression of DNA methyltransferases (DNMTs) and cell growth in pancreatic cancers.

Materials and methods

For in vitro ¹²⁵I 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 ¹²⁵I 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 ¹²⁵I seed implantation, in vivo 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 ¹²⁵I seed implantation.

Results

¹²⁵I 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 ¹²⁵I 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.

Conclusion

¹²⁵I 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.

【 授权许可】

   
2011 Ma et al; licensee BioMed Central Ltd.

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