Abstract: To explore the regulatory effect of 9R-P49 peptide on FoxM1 and its preliminary mechanism on fibroblast L929 cells, CCK-8 was used to detect cell inhibition rate, AO/EB double staining and flow cytometry to detect cell apoptosis, transwell assay to detect cell migration and cell plate clone to detect cell proliferation. The potential binding sites of the P49 peptide to FoxM1-DNA binding domain（FoxM1-DBD） were predicted using PyMOL molecular docking software. Mouse fibroblast L929 cells were treated with 0, 30.0 and 60.0 μg/mL 9R-P49 peptide and the expression of FoxM1 protein was detected by Western Blot. Finally, the differential expressed genes and related pathways were analyzed by RNA transcriptome. The results showed that 9R-P49 could inhibit FoxM1 protein expression in L929 cells. At the same time, 9R-P49 could inhibit cell proliferation and promote cell apoptosis of L929 cells. P49 peptide binds potentially to the Arg 297, Ser 290 and Asp 293 sites on FoxM1-DBD. The GO classification of differentially expressed genes in the transcriptome after drug treatment was mainly enriched in cellular process, single-organism process, biological regulation, and metabolic process. The KEGG classification was mainly enriched in the immune system, endocrine system, signal transduction, and metabolism pathways. In conclusion, 9R-P49 can inhibit the proliferation of L929 cells and promote apoptosis by regulating the expression of FoxM1 in L929 cells.

Key words: 9R-P49, FoxM1, fibrosis, transcriptome, polypeptide