2013 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	24791431
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Kyushu University
Principal Investigator	ONIMARU Manabu 九州大学, 医学(系)研究科(研究院), 共同研究員 (80529876)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	膵癌 / HDAC1 / DNA / Double Strand Break / Trichostatin A / iRNA
Research Abstract	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.