Development of novel molecular therapy target at epigenetics against salivary gland cancer

Research Project

Project/Area Number	24593035
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Surgical dentistry
Research Institution	The University of Tokushima
Principal Investigator	OHE Go 徳島大学, 大学病院, 助教 (60432762)
Co-Investigator(Kenkyū-buntansha)	UCHIDA Daisuke 獨協医科大学, 医学部, 准教授 (20335798) TAMATANI Tetsuya 徳島大学, 大学病院, 講師 (30274236) TAKAMARU Natsumi 徳島大学, 大学病院, 助教 (40513031) NAGAI Hirokazu 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (50282190) KURIBAYASHI Nobuyuki 徳島大学, ヘルスバイオサイエンス研究部, 助教 (80617332)
Project Period (FY)	2012-04-01 – 2015-03-31
Project Status	Completed (Fiscal Year 2014)
Budget Amount *help	¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000) Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	HDAC阻害剤 / バルプロ酸 / 唾液腺癌 / 細胞周期
Outline of Final Research Achievements	Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time- and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC.