Development of a new therapeutic method for drug resistant choriocarcinoma by focusing on apoptosis by homocysteine

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16767
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya University
• Principal Investigator: Nishino Kimihiro 名古屋大学, 医学系研究科, 准教授 (80801448)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ホモシステイン / 葉酸代謝 / アポトーシス / 難治性癌 / 絨毛癌

Outline of Final Research Achievements

This study was performed to investigate the following two things in order to improve the efficacy of the treatment of drug resistant choriocarcinoma and to develop a new therpeutic method. One is whether homocysteine can introduce apoptosis of choriocarcinoma cells which are malignant form of trophoblastic cells. The other is whether an increase in homocysteine concentration is contributed to kill choriocarcinoma cells when MTX is administered. This study illustrated that homocysteine introduced apoptosis of choriocarcinoma cells. This study also demonstrated that homocysteine concentration was increased in supernatant of choriocarcinoma cells when MTX is administered, and that homocysteine concentration was not increased in supernatant of resistant choriocarcinoma cells. This study evidenced that an increase in homocysteine concentration was contributed to kill choriocarcinoma cells when MTX was administered.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

絨毛癌患者のうち、約15％の患者は化学療法抵抗性に陥り、寛解に至らずに死亡するため、既存の化学療法とは異なる機序にもとづく新規治療法の開発が強く望まれていた。絨毛癌細胞の葉酸代謝に着目した本研究により、ホモシステインが絨毛癌細胞のアポトーシスを誘導しうることが証明された。このことから、難治性絨毛癌に対する新規治療法として、ホモシステインを応用したものを開発する基盤が確立された。以上の研究成果は、第76回日本産科婦人科学会で発表され、今後のさらなる研究の発展に対する学術的、社会的意義は大きく、難治性絨毛癌の治療成績向上に貢献しうると考えられる。