Drug resistance and calcium signaling in cancer cell line

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16338
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Iwate Medical University
• Principal Investigator: Hiraki Hayato 岩手医科大学, 医歯薬総合研究所, 助教 (50847358)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: カルシウムシグナル / 薬剤耐性 / がん細胞株

Outline of Final Research Achievements

Ca2+ signal acts as a second messenger in living organism. In this study, we focused on the Ca2+ signal in cancer cells, especially on anti-cancer drug resistance. Ca2+ signals were observed under a laser scanning confocal microscope. We found that 5-Fluorouracil (5-FU) induced Ca2+ uptake, and the efflux speed was more quickly in 5-FU tolerant cell line than that of parental cell. siRNA which targeted PMCA family slightly reduced the protein expression level of the Ca2+ pump but changed the Ca2+ signal from 5-FU tolerant type to parental type in MKN45 5-FU tolerant cell line. In addition, there was weak correlation between the expression level of PMCA and 5-FU resistance in gastric cancer cell lines. These results suggested that PMCA family Ca2+ pumps may be contributed to the early 5-FU response in gastric cancer cells.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

Ca2+シグナルは生物に広く保存される基本的な生命現象である。一方で、がん細胞におけるCa2+シグナル、特に抗がん剤誘導性のCa2+シグナルはほとんど着目されてこなかった。本研究では、5-フルオロウラシル抵抗性胃癌細胞株において、特徴的なCa2+シグナルが誘導される発見を足掛かりに、薬剤抵抗性株の特徴を規定する因子としてPMCAファミリーCa2+ポンプを同定した。一般に薬剤抵抗性の再発がんは難治性である。治療標的の候補の探索はもちろん、薬剤抵抗性獲得メカニズムの一端を明らかにすることは、未治療のがん細胞が薬剤抵抗性を獲得しないよう阻害する手段を検討することにつながる。