生物学杂志

生物学杂志 ›› 2025, Vol. 42 ›› Issue (2): 40-.doi: 10.3969/j.issn.2095-1736.2025.02.040

• 研究报告 • 上一篇    下一篇

二甲双胍联合放化疗诱导线虫生殖腺细胞凋亡及机制研究

韩天怡1,2， 赵喜朋1,2， 赵国平2， 王茹茹2   

  1. 1. 中国科学技术大学 研究生院科学岛分院， 合肥 230036；
    2. 中国科学院合肥物质科学研究院 强磁场科学中心， 合肥 230031
  • 出版日期:2025-04-18 发布日期:2025-04-14
  • 通讯作者: 王茹茹，博士，博士后，研究方向为生物物理学，E-mail:wangruru@mail.ustc.edu.cn；赵国平，博士，研究员，研究方向为生物物理学，E-mail:gpz@ipp.ac.cn；王茹茹和赵国平为共同通信作者
  • 作者简介:韩天怡，硕士研究生，研究方向为生物物理学，E-mail:sa21168387@mail.ustc.edu.cn
  • 基金资助:
    国家自然科学基金项目（32171240）

The mechanism of apoptosis of gonadal cells induced by metformin combined with chemoradiotherapy and inhibition of vulva tumor in nematodes

HAN Tianyi1,2, ZHAO Xipeng1,2, ZHAO Guoping2, WANG Ruru2   

  1. 1. Science Island Branch of Graduate School, University of Science and Technology of China, Hefei 230036, China;
    2. High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences,
    Hefei 230031, China
  • Online:2025-04-18 Published:2025-04-14

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摘要： 为了探讨二甲双胍联合放化疗法诱导秀丽隐杆线虫生殖腺细胞凋亡的作用机制，选用野生型与egl-1、ced-3、ced-4、hus-1、cep-1基因缺陷的线虫品系，用荧光染料法检测二甲双胍联合50 Gy辐照或顺铂处理后野生型及突变型线虫生殖腺细胞的凋亡数量，qPCR法检测缺陷相关基因的表达量，显微镜下观察let-60线虫的阴门肿瘤。1 mmol/L二甲双胍增加了辐射及100 μmol/L顺铂诱导的野生型线虫生殖腺细胞凋亡；机制上发现，核心凋亡基因egl-1、ced-4、ced-3及DNA损伤应答基因hus-1、cep-1介导了二甲双胍增加辐射及顺铂诱导的生殖腺细胞凋亡信号。此外，二甲双胍联合顺铂有效抑制了let-60线虫阴门肿瘤的发展。结果表明，二甲双胍增加了放化疗诱导的线虫生殖腺细胞凋亡，而DNA损伤应答通路、核心凋亡通路参与了二甲双胍调控的放化疗敏感性过程。

关键词: 二甲双胍, 秀丽隐杆线虫, 生殖腺细胞, 细胞凋亡, 放化疗

Abstract: To explore the mechanism of metformin combined with radiotherapy and chemotherapy-induced apoptosis inCaenorhabditis elegansgerm cells, wild-type and mutant strains with defects inegl-1, ced-3, ced-4, hus-1,andcep-1genes were selected. Fluorescence staining was used to detect the apoptosis levels of germ cells in wild-type and mutant worms after treatment with metformin combined with 50 Gy irradiation or cisplatin. qPCR was used to measure the expression levels of genes related to defects, and the development of vulval tumors inlet-60worms was observed under a microscope. 1 mmol/L metformin increased the apoptosis of germ cells induced by radiation and 100 μmol/L cisplatin in wild-type worms. Mechanistically, core apoptosis genesegl-1, ced-4, ced-3,and DNA damage response geneshus-1, cep-1mediated the apoptosis signals induced by metformin in combination with radiation and cisplatin. Additionally, metformin combined with cisplatin effectively inhibited the development of vulval tumors inlet-60worms. These results indicated that metformin increased apoptosis of germ cells induced by radiotherapy and chemotherapy, and DNA damage response pathways and core apoptosis pathways were involved in the process of metformin-regulated sensitivity to radiotherapy and chemotherapy.

Key words: metformin;Caenorhabditis elegans, gonadal cell, apoptosis, chemoradiothe

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