The sensitizing anti-cancer effect of intra-arterial infusion of carbon dioxide-saturated solution in a rabbit VX2 liver tumor model

Research Project

Project/Area Number	16K10349
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Radiation science
Research Institution	Kobe University
Principal Investigator	YAMAGUCHI Masato 神戸大学, 医学部附属病院, 准教授 (10457096)
Co-Investigator(Kenkyū-buntansha)	上嶋英介神戸大学, 医学部附属病院, 助教 (40645561) 岡田卓也神戸大学, 医学部附属病院, 特命講師 (80514786) 杉本幸司神戸大学, 医学部附属病院, 特命教授 (90314476) 祖父江慶太郎神戸大学, 医学部附属病院, 講師 (90622027)
Research Collaborator	KATAYAMA Naoto
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	炭酸ガス / 動注化学療法 / 抗癌剤増感作用 / 動脈内炭酸ガス注入 / 医学 / がん / IVR
Outline of Final Research Achievements	This study aimed to evaluate the efficacy of an intra-arterially infused carbon dioxide (CO2)-saturated solution in sensitizing the anti-cancer effect of cisplatin in a rabbit VX2 liver tumor model. Forty VX2 liver tumor-bearing Japanese white rabbits were randomly divided into four groups and infused via the hepatic artery with a saline solution (control group, CO2 group, cisplatin group, and combined group). The tumor growth ratios were calculated on days 3 and 7. Hypoxia (HIF-1α) and apoptosis (cleaved caspase-3) were evaluated on day 7. The tumor growth ratio was significantly lower in the CO2 group than in the control group (day 3), and in the combined group than in the cisplatin group (days 3 and 7). HIF-1α suppression and increased cleaved caspase-3 expression were detected in the CO2 and combined groups, compared with the other two groups. An intra-arterially infused CO2-saturated solution inhibits liver VX2 tumor growth and sensitizes the anti-cancer effect of cisplatin.
Academic Significance and Societal Importance of the Research Achievements	本研究においてウサギ腫瘍モデルに対する炭酸飽和水動注療法の有効性が示唆され、炭酸ガス研究の発展に寄与するものと考えられる。また炭酸飽和水動注療法の安全性や有効性をさらに研究し、実臨床への使用が可能となれば、肝細胞癌を始めとした肝腫瘍に対する動注化学療法において容易かつ安価に腫瘍の治療効果を高めることが可能となり、臨床的意義は非常に高いものと考えられる。