Comparison in acquired and natural resistance mechanisms to decitabine in colorectal cancer cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18942
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Hosokawa Mika 神戸薬科大学, 薬学部, 助教 (70548271)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: デシタビン / DNAメチル基転移酵素阻害薬 / 大腸がん / 獲得耐性 / 自然耐性 / deoxycytidine kinase

Outline of Final Research Achievements

By long-term exposure of decitabine (DAC), a DNA methyltransferase inhibitor, human colorectal cancer (CRC) cell lines, HCT116 and SW620 cells acquired resistance to DAC. It was clarified that the decrease in deoxycytidine kinase (dCK, activation enzyme of DAC) is mainly involved in acquired resistance to DAC. In contrast, another human CRC cell line, HT29 cells were suggested to show natural resistance to DAC by some factors other than dCK. In microarray analysis, the up-regulation in metabolism of xenobiotics by P450, lipid metabolism and WNT signaling pathway was observed in HT29 cells. Detail examination of these pathways found in this research would be helpful for the overcoming of resistance to DAC.

Free Research Field

生物薬剤学