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  

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

作　　者：韩天怡 赵喜朋 赵国平 王茹茹 HAN Tianyi;ZHAO Xipeng;ZHAO Guoping;WANG Ruru(Science Island Branch of Graduate School,University of Science and Technology of China,Hefei 230036,China;High Magnetic Field Laboratory,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031,China)

机构地区：[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　　处：《生物学杂志》2025年第2期40-45,共6页Journal of Biology

基　　金：国家自然科学基金项目(32171240)。

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100μmol/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。To explore the mechanism of metformin combined with radiotherapy and chemotherapy-induced apoptosis in Caenorhabditis elegans germ cells,wild-type and mutant strains with defects in egl-1,ced-3,ced-4,hus-1,and cep-1 genes 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 in let-60 worms was observed under a microscope.1 mmol/L metformin increased the apoptosis of germ cells induced by radiation and 100μmol/L cisplatin in wild-type worms.Mechanistically,core apoptosis genes egl-1,ced-4,ced-3,and DNA damage response genes hus-1,cep-1 mediated the apoptosis signals induced by metformin in combination with radiation and cisplatin.Additionally,metformin combined with cisplatin effectively inhibited the development of vulval tumors in let-60 worms.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.

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 

分 类 号：Q25[生物学—细胞生物学]