Development of the new radiation therapy using tumor suppressor gene NPRL2 for esophageal cancer

利用抑癌基因NPRL2开发食管癌新放射疗法

• 批准号: 20591575
• 负责人: UEDA Kentaro
• 金额: $ 2.25万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591575/
• 关键词: NPRL2遺伝子; 食道癌; 放射線治療; 遺伝子; 癌; 放射線科; 放射線

In 10 human esophageal cancer cell lines, the IC50 of radiation ranged from IC50 1.58Gy to 9.28Gy. There were no expression of NPRL2 protein in these cell lines, on the other hand, Rad51 protein showed strong expression in all cell lines. The levels of NPRL2 or Rad51 expression did not correlate with radiosensitivity. Tumor growth inhibition rate of NPRL2 vector was about 30% for human esophageal cancer cells, and combination therapy of NPRL2 vector and IC20 of radiation therapy enhanced this inhibitory effect to around 60 percent. We prepared some Rad51-siRNA vectors, however, these Rad51-siRNA vector did not inhibit expression of Rad51 protein. To investigate the mechanism of combined effect of NPRL2 vector, we made four groups ; 1) control group, 2) radiation therapy (IC20), 3) NPRL2 group, 4) NPRL2+radiotherapy. NPRL2+radiation therapy groupactivated DNA damage pathway, and showed a strong G2 arrest and apoptosis, compared with the other group.

10株人食道癌细胞系的IC50为1.58~9.28Gy.NPRL2蛋白在这些细胞系中均无表达，而RAD51蛋白在所有细胞系中均有强表达。NPRL2和RAD51的表达水平与放射敏感性无关。NPRL2载体对人食道癌细胞的抑瘤率约为30%，NPRL2载体与IC20联合放射治疗可使抑瘤率提高至60%左右。我们制备了一些RAD51-siRNA载体，但这些载体并不抑制RAD51蛋白的表达。为了探讨NPRL2载体的联合作用机制，我们设4组：1)对照组，2)放疗(IC20)组，3)NPRL2组，4)NPRL2+放疗组。NPRL2+放射治疗组激活了DNA损伤通路，表现出较强的G2期停滞和细胞凋亡。