Valproic acid inhibits irradiation-induced epithelial-mesenchymal transition and stem cell-like characteristics in esophageal squamous cell carcinoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kanazawa University
• Principal Investigator: Itasu Ninomiya 金沢大学, 大学病院, 准教授 (60345618)
• Co-Investigator(Kenkyū-buntansha): 藤村 隆 金沢大学, 医学系, 准教授 (50262580)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 食道癌 / 放射線治療 / 放射線耐性 / 放射線感受性 / バルプロ酸

Outline of Final Research Achievements

We investigated the mechanism of radio-resistance and the anti-radioresistant and radiosensitizing effect of classic histone deacetylase (HDAC) inhibitor valproic acid (VPA) in esophageal squamous cell carcinoma (ESCC) cells. First, we showed that 2 Gy of irradiation induced epithelial–mesenchymal transition (EMT) and cancer stem-like cell properties in ESCC TE9 cells. In addition, irradiation enhanced invasion and migration ability with upregulation of matrix metalloproteinases. Second, we found that VPA induced reversal of EMT caused by irradiation in TE9 cells, resulting in attenuated cell invasion and migration abilities. Third, VPA induced Ku70 acetylation and prolonged γH2AX levels after irradiation in three ESCC cell lines (KES, TE9, TE10). Our results suggest that VPA inhibit radiation induced EMT and show radiosensitizing effect by inhibiting DNA double strand break repair pathway in ESCC.

Free Research Field

食道癌治療