Elucidation of the radioresistance mechanism on the microenviroment of pancreatic cancer and control of the stroma cells causing radioresistance by newly artificial virus.

阐明胰腺癌微环境的放射抗性机制以及新型人工病毒对引起放射抗性的基质细胞的控制。

• 批准号: 24791431
• 负责人: ONIMARU Manabu
• 金额: $ 2.75万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24791431/
• 关键词: 膵癌; HDAC1; DNA; Double Strand Break; Trichostatin A; iRNA; 放射線抵抗性; NG2; PDGFRβ; 低酸素環境; CTGF

Pancreatic ductal adenocarcinoma (PDA) is characterised by aggressive tumor spread, early metastasis and a poor prognosis. Standard therapy for PDA patients includes not only surgery and chemotherapy but also radiotherapy. However, there have been few detailed molecular biological studies to investigate about the effect of radiotherapy on PDA. It was reported that histone deacetylase 1 (HDAC1) is responsible for DNA repair of double strand breaks after irradiation in human fibroblasts. Here, we examined HDAC1 is involved in the mechanism of radioresistance of PDA. The irradiated pancreatic cancer cell lines reduced the radiosensitivity and increased the HDAC1 mRNA expression. The radioresistance was decreased after the addition of low-concentration TSA or knockdown of HDAC1 in pancreatic cancer cell lines. The present data suggested that HDAC1 is invoved in the mechanism of the radioresistance of pancreatic cancer cells.

摘要胰导管腺癌（Pancreatic ductal adencarcinoma， PDA）的特点是肿瘤扩散严重，转移早，预后差。PDA患者的标准治疗不仅包括手术和化疗，还包括放疗。然而，目前还没有详细的分子生物学研究来探讨放疗对PDA的影响。据报道，组蛋白去乙酰化酶1 （HDAC1）参与了人成纤维细胞辐照后DNA双链断裂的修复。在这里，我们研究了HDAC1参与PDA放射耐药的机制。照射后的胰腺癌细胞系放射敏感性降低，HDAC1 mRNA表达升高。添加低浓度TSA或敲低HDAC1后，胰腺癌细胞株的放射抗性降低。目前的数据表明，HDAC1参与了胰腺癌细胞放射耐药的机制。

项目成果

Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor

• DOI: 10.1016/j.jss.2012.06.051
• 发表时间: 2013-05-15
• 期刊: JOURNAL OF SURGICAL RESEARCH
• 影响因子: 2.2
• 作者: Eguchi, Daiki;Ikenaga, Naoki;Tanaka, Masao
• 通讯作者: Tanaka, Masao

膵癌細胞株におけるHiston deacetylase1の放射線耐性に関する評価

胰腺癌细胞系组蛋白脱乙酰酶1的放射抗性评价

• 作者: 田中友晴;他
• 通讯作者: 他

Histon Deacetylase 1 is Responsible for Radioresistance of Pancreatic Cancer cells

组蛋白脱乙酰酶 1 负责胰腺癌细胞的放射抗性

• 发表时间: 2013
• 作者: Tanaka T;Ohuchida K;Mizumoto K;Kozono S;Tanaka M
• 通讯作者: Tanaka M