Clarification of the lipid metabolism concerning progression of gastrointestinal cancer, followed by developing new therapy.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462062
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: ISHIKAWA Shinji 熊本大学, 医学部附属病院, 非常勤診療医師 (80419639)
• Co-Investigator(Kenkyū-buntansha): BEPPU Touru 熊本大学, 医学部附属病院, 特任助教 (70301372) ; WATANABE Masayuki 公益財団法人がん研究会, その他部局等, 食道担当部長 (80254639)
• Research Collaborator: TOKUNAGA Ryoma 熊本大学, 大学院生命科学研究部, 大学院生 ; HIGASHI Takaaki 熊本大学, 大学院生命科学研究部, 大学院生 ; OHUCHI Mayuko 熊本大学, 大学院生命科学研究部, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: スタチン / 大腸癌 / EZH2 / HDAC5 / p27 / MEK/ERK

Outline of Final Research Achievements

We have found out that the anti-tumor effect of statins (a therapeutic drug for hyperlipidemia) against colon cancer cell lines was different to the type of statin. We also discovered that this mechanism was not related to the mevalonate cascade (the major pathway of statins) but associated with the decrease expression of EZH2 (a molecule related to DNA methylation) that were found to be due to increased expression of p27.
Though the mechanism how statins regulate EZH2 expression is unknown , from the relation between the number of cells killed by statin administration and the expression level of the molecules involved in cell proliferation by statin administration, the possibility that statins have dual kinase inhibitory effect are suggested. We are now investigating a new treatment strategy by targeting this pathway.

Free Research Field

消化器外科