Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice
Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106, effectively suppresses the growth of tumor cells transplanted in mice
复制标题
DOI：
10.1016/j.ijrobp.2006.12.061
复制
发表时间：
2007-05-01
影响因子：
7
通讯作者：
Kumwabara, Mikinori
中科院分区：
文献类型：
--
作者：
Yasui, Hironobu;Inanami, Osamu;Kumwabara, Mikinori
目的：为了检查X射线照射与核糖核苷抗癌药物1-脱氧核糖核苷（1-脱氧核糖核苷）联合给药的体内抗肿瘤疗效，（3-C-乙炔基-beta-D-呋喃核糖基）胞嘧啶方法和材料：将Colon 26小鼠直肠腺癌细胞和MKN 45人胃腺癌细胞分别接种于BALB/c小鼠和严重联合免疫缺陷小鼠的足垫。用相对低剂量的X射线（2戈伊）和低剂量的TAS 106（0.1 mg/kg和0.5 mg/kg）处理。通过测量Colon 26第5天至第16天的肿瘤体积和MKN 45第7天至第20天的肿瘤体积来监测肿瘤生长。采用Ki-67免疫组化和末端脱氧核苷酸转移酶介导的缺口末端标记染色对肿瘤中的增殖和凋亡细胞进行组织学分析。Survivin的表达，一个关键的分子相关的肿瘤生存，进行了评估，通过定量聚合酶链反应和免疫组化analysis.Results：当X射线照射和TAS 106治疗相结合，显着抑制肿瘤生长观察到在这两种类型的肿瘤与X射线照射或TAS 106单独治疗的小鼠相比。在以2天间隔接受三次联合治疗的小鼠中，观察到一半的小鼠肿瘤生长受到显著抑制。与此同时，Survivin的表达受到抑制，Ki-67阴性细胞和凋亡细胞出现。结论：X射线照射和TAS 106能有效抑制小鼠肿瘤的生长。TAS 106对Survivin表达的抑制被认为主要有助于抑制肿瘤生长。(c)2007年爱思唯尔公司
Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice.Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis.Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed.Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth. (c) 2007 Elsevier Inc.