Inhibitory Effect Of Peptide M1-138 On FOXM1 Tumor Stem Cell Subsets

Breast cancer is one of the malignant tumors that threaten human health,and more than 1 million people die of breast cancer worldwide each year.The tumor tissue is composed of heterogeneous cell populations,in which there are very few tumor stem cells,which are the roots of tumor proliferation,metastasis and recurrence.It is one of the root causes of tumor cell heterogeneity.Therefore,studying the nature of different cell subpopulations in the same tumor,especially tumor stem cell subpopulations,is of great signif icance for understanding the molecular mechanism of breast cancer stem cell characteristics and for discovering new therapeutic targets and pathways.Studies have shown that FOXM1 not only participates in the regulation of tumor cell cycle regulation,angi ogenesis,tumor cell invasion and metastasis,but also plays an important role in the development of tumor stem cells.This article focuses on the inhibitory effect of peptide M1-138 on the subpopulation of FOXM1 overexpressing cells in breast cancer MDA-MB-231.Through the visualization method of intracellular FOXM1 expression,the FOXM1promoter constructed by our research group carried the lentiviral vector（Lv-Promoter FOXM1-EGFP）carrying EGFP green fluorescent protein to infect the human breast cancer cell line MDA-MB-231.Express EGFP as the standard,Lv-Promoter FOXM1-EGFP-infected MDA-MB-231 cells were subjected to flow sorting to obtain a FOXM1^High cell subpopulation,while EGFP-negative cells were collected as a control cell subpopulation.The obtained FOXM1^Low,FOXM1^Hightwo cell subpopulation samples,Western Blot confirmed that EGFP expression was synchronized with FOXM1.After the flow cytometry sorted out the FOXM1high-expressing cell subpopulation and the FOXM1 low-expressing cell subpopulation in the MDA-MB-231 cell line,they were cultured with microspheres respectively,and q RT-PCR and Western blot were used to detect dry markers.The highly expressed subpopulation of cells has the characteristics of self-renewing tumor stem cells,and at the same time treated with paclitaxel anticancer drugs,it was found that the highly expressed subpopulation of FOXM1 cells have higher resistance to paclitaxel.Reuse the FOXM1 nitrogen-terminal recombinant protein（M1-138 peptide drug）developed by this group that can inhibit FOXM1 transcription activity and interfere with FOXM1 and its protein interactions,and treat FOXM1^Highsubpopulation cells obtained from MDA-MB-231 With FOXM1^Low subpopulation control cells,trypan blue staining,CCK8 and other experiments were used to detect cell viability,and the inhibitory effect of M1-138 peptide on FOXM1^Highsubpopulation cells and FOXM1^Low subpopulation was investigated.The results of this experiment suggest that to understand the development of drugs that use FOXM1as a target for tumor therapy and to suppress the stemness of breast cancer cells,lay the experimental foundation.