The quest for the appropriate anesthetic agents for patients undergoing cancer surgery-What is the best analgesic agent?

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09367
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Hirosaki University
• Principal Investigator: NIWA HIDETOMO 弘前大学, 医学研究科, 准教授 (20374845)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: natural killer cell / 抗癌免疫 / レミフェンタニル / オピオイド / 癌手術

Outline of Final Research Achievements

As an integral part of innate immunity, natural killer (NK) cells kill cancer cells. Thus, the NK cell cytotoxicity (NKCC) suppressed by surgical stress during cancer surgery may be associated with poor outcomes. Remifentanil could attenuate the NKCC suppression after cancer surgery due to its strong anti-nociceptive action. However, the effect of remifentanil on the NKCC is unknown. The aim of this study was to investigate such effect of remifentanil. We established the in vitro experiment model using human cell lines (the cell line K562 as target cells and the NK cell line KHYG1as effecter cells). The NK cells were treated with 3-60 nM remifentanil (the remifentanil groups) or without remifentanil (the control) for 24 h. The post-treatment NKCC was measured with a lactate dehydrogenase assay and compared among the treatment groups. The dose dependent reduction of NKCC was found in the remifentanil groups.

Free Research Field

臨床麻酔

Academic Significance and Societal Importance of the Research Achievements

レミフェンタニルは、癌手術における標準的な鎮痛薬であり、日本の外科手術において最も使用頻度が高い麻薬鎮痛薬であるが、その抗癌免疫であるNatural killer cell活性（NKCC）への影響についての研究データは、基礎研究レベルから不足している。今回、我々はヒトNK細胞株を用いた基礎研究モデルを確立し、レミフェンタニルがNKCCを用量依存性に抑制することを明らかにした。生来のヒトNK細胞は、培養が難しく、多くの実験を行えないことが問題だったが、今回、培養が容易なヒトNK細胞株を使用してこの問題を解決した。このことは、今後、さらに詳細な基礎実験を行う上での利点となる。