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