2021 Fiscal Year Final Research Report

Cancelation of Warburg effect and anti cancer effect of pancreatic cancer cells by intracellular phospholipase A1.

Research Project

PDF

Project/Area Number	19K07088
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research Institution	Teikyo University
Principal Investigator	Yamashita Atsushi 帝京大学, 薬学部, 教授 (80230415)
Co-Investigator(Kenkyū-buntansha)	松本直樹帝京大学, 薬学部, 助教 (40447834) 佐々木洋子帝京大学, 薬学部, 講師 (90324110)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	DDHD1 / ホスホリパーゼA1 / ワールブルグ効果 / ミトコンドリア呼吸 / 細胞生存 / 抗がん剤 / リン酸化修飾 / 細胞内局在変化
Outline of Final Research Achievements	The effect of intracellular phospholipase A1 on the survival of pancreatic cancer cells was examined. The expression of DDHD1/PA-PLA1 reduced the cell growth and survival of PACN-1 cells through the arrest in the G2 in the cell cycle. The expression of DDHD1 also increased the respiration of mitochondria. DDHD1 also increased the sensitivity of anti-cancer drug. In cancer cells including pancreatic cancer cells, the glycolysis produces ATP for growth but respiration in mitochondria is lowered. This metabolic change is termed the “Warburg effect”. The cancelation of the “Warburg effect” by the expression of DDHD1 caused the reduced survival of PACN-1 cells. The pharmacological agent sodium dichloroacetate also canceled the “Warburg effect” and reduced the survival and increased the sensitivity of anti-cancer drug. The elucidation　of the mechanism of cancelation of the “Warburg effect” by DDHD1 phospholipase A1 will read to a novel strategy against intractable cancer.
Free Research Field	生化学、分子生物学
Academic Significance and Societal Importance of the Research Achievements	膵臓がんは抗がん剤が効きにくく、5年生存率が極めて低い。本研究は、細胞内ホスホリパーゼA1（PLA1）のDDHD1を発現させると、がん細胞の“ワーブルグ効果”を解除し、抗がん剤の感受性が亢進することを見出した。DDHD1の“ワーブルグ効果”解除のメカニズムを明らかにすることは、難治がんの制圧の緒になることが考えられる。メカニズム解明のひとつとしてDDHD1のリン酸化と細胞内局在変化を調べた。