Application of photodynamic therapy of cisplatin-resistant cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Horibe Sayo 神戸薬科大学, 薬学部, 講師 (50389110)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: シスプラチン耐性

Outline of Final Research Achievements

The acquired cisplatin (CDDP) resistance is a major obstacle to successful treatment. In this study, we examined the mechanisms underlying acquired CDDP resistance using ACR20 cells, which are CDDP -resistant cells derived from A549 lung cancer cells. Reactive oxygen species (ROS) levels were elevated in ACR20 cells no treated with CDDP. Notably, evaluation of mitochondrial oxygen consumption rate and mitochondrial superoxide levels revealed a deterioration of mitochondrial function in ACR20 cells. Mitochondrial DNA PCR-RFLP analysis revealed four mutations with varying percentage levels in ACR20 cells. Analysis of three-dimensional structure data indicated that a mutation (ND2 F40L) may impact the proton translocation pathway, thereby affecting mitochondrial complex I activity. Together, these findings suggest that intrinsic ROS levels were elevated by loss of mitochondrial function via mitochondrial DNA mutations, which decreased the sensitivity to CDDP in ACR20 cells.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究において、シスプラチン耐性獲得機構にミトコンドリアDNA変異によるミトコンドリア機能低下が関与していることを明らかにした。本研究結果は、シスプラチンに対する耐性を示したがんの治療において、新しい治療標的を提唱することができ、またシスプラチンに対する感受性を評価するためのバイオマーカーとしてミトコンドリアDNAに着目することの意義を提案することができた。