Department of Gastroenterology, The Changhai Hospital, The Second Military Medical University, Shanghai, PR China.
J Exp Clin Cancer Res. 2011 Apr 2;30(1):35. doi: 10.1186/1756-9966-30-35.
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.
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.
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.
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.
碘 125（125I）种子照射是治疗不可切除胰腺癌的有效方法。然而，近距离放射治疗的放射生物学机制尚不清楚。因此，我们研究了连续低能 125I 照射对胰腺癌细胞凋亡、DNA 甲基转移酶（DNMTs）表达和细胞生长的影响。
体外 125I 种子照射时，SW-1990 细胞分为三组：对照组（0Gy）、2Gy 组和 4Gy 组。建立胰腺癌动物模型，将 SW1990 细胞手术植入小鼠胰腺。植入后 10d，30 只胰腺癌小鼠行 125I 种子植入，分为三组：0Gy 组、2Gy 组和 4Gy 组。照射后 48 或 72h 时，采用流式细胞术检测细胞凋亡；实时 PCR 和 Western blot 分析分别检测 DNMTs mRNA 和蛋白表达变化。照射后 28d，采用 TUNEL 染色检测体内细胞凋亡，免疫组化染色检测 DNMTs 蛋白表达。0d 和 28d 时测量肿瘤体积。
125I 种子照射诱导明显的细胞凋亡，尤其在 4Gy 时更明显。2Gy 组的 DNMT1 和 DNMT3b mRNA 和蛋白表达明显高于对照组。相反，4Gy 细胞组的 DNMT3b mRNA 和蛋白表达明显低于对照组。125I 种子植入治疗组的 TUNEL 阳性细胞明显多于对照组，尤其是在 4Gy 时。4Gy 种子植入组的 DNMT1 和 DNMT3b 蛋白染色明显弱于对照组。因此，125I 种子植入抑制了肿瘤生长，减小了肿瘤体积。
125I 种子植入可杀伤胰腺癌细胞，尤其在 4Gy 时更明显。125I 诱导的凋亡和 DNMT1、DNMT3b 表达的变化提示近距离放射治疗有效的潜在机制。
