Assessment of overcoming effect for multidrug resistance with photodynamic therapy for esophageal cancer and development of newly combination treatment with chemotherapy and photodynamic therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17694
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: University of Miyazaki
• Principal Investigator: Kai Kengo 宮崎大学, 医学部, 助教 (90851585)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 光線力学療法 / 薬剤耐性軽減効果 / talaporfin sodium / 未分化型胃癌細胞株 / 腹膜播種

Outline of Final Research Achievements

In this study, we conducted immunohistochemistry using clinical samples of esophageal cancer and cell culture to verify the effect of low-intensity photodynamic therapy (PDT) in reducing chemoresistance. With clinical samples, we quantified and compared the expression of breast cancer resistance protein (BCRP) before and after treatment using Image-J software, evaluating the staining intensity of BCRP in the nucleus and cytoplasm of tumor cells. However, we did not observe any significant differences in BCRP expression between pre- and post-treatment for both the nucleus (p=0.459) and cytoplasm (p=0.313). On the other hand, we confirmed that combining low-intensity PDT with the cytotoxic anticancer agent laserfirin for undifferentiated gastric cancer cell lines could improve drug sensitivity to the level of differentiated gastric cancer cell lines.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

PDTの新しいメカニズムである低強度TS-PDT付加による薬剤感受性改善効果（photodynamic priming effect）を未分化型胃癌細胞株を用いたin vitro実験で明らかにした。次なるステップとして、TS-PDP後の胃癌細胞株を用いた治療耐性因子（薬剤排泄トランスポーター、癌幹細胞マーカーなど）の挙動を免疫組織化学やPCR法で評価し、腹膜播種モデルマウスを用いたPDP効果の検証を行うことで、従来の癌治療では効果が得られなかった胃癌腹膜播種などの難治性癌に対する新たな治療法を開発したい。