Design And Study Of Anti-cancer Leading Drugs Based On Foxmlc

As one of transcription factors of Fox family, FoxM1c plays an important role in regulating normal cells division, but the abnormal expression of FoxM1c can also lead to the occurrence and development of tumor cells. Many studies have confirmed that FoxM1sustained high expression in a variety of tumor cells, but not in normal cells without proliferation. Therefore, by targeting FoxM1protein to treat tumors is feasible in theory, but due to the characteristics of transcription factors and lack of hydrophobic structure, which makes the traditional small molecule chemical drugs difficult to target, targeting FoxM1has not made substantial progress. With the development of biotechnology, peptide drugs overcoming the inherent shortcomings of traditional medicines have made targeting FoxM1become possibilities. Natural herbal contains a variety of ingredients which can targeting multiple targets, exactly corresponding to the characteristics of multiple pathways and targets in tumorigenesis.First, based on the lab’s previous work of high affinity phage peptide sequences obtained by screening random peptide library, we used the MEME software to obtain a high affinity peptide sequences:WHLD. Then, through fusing the motif with penetrating peptide, finally two peptides sequences CT-788: rrrrrrrrGSGSWHLD and CT-789: WHLDGSGSWHLD have been determined. Before synthesis, we apply Molegro.Virtual.Docker(MVD) to simulate interactions of two peptides and the receptor protein FoxM1c DNA domain, which shows stable binding with both two peptides.CT-788and CT-789peptides were designed and in vitro study revealed that the viability of HEPG-2cancer cells could be reduced to41.26%and15.96%at the concentration of100μg/ml of the peptides, respectively. In addition, the viability of MCF-7cancer cells could be reduced to34.26%and17.80%at the concentration of100μg/ml of the peptides, respectively.The natural plantliquid YN-01can inhibit the growth of HEPG-2cells and can kill cells at4%. MTT experimental data has also illustrated that the inhibition rate of HEPG-2can reach at68%under4%concentration treated by YN-01. On this basis, further study. by agarose gel electrophoresis, AO-EB and flow cytometry, it was determined that YN-01could induce HEPG-2cells into apoptosis. Finally, quantitative PCR experiments has showed that24hours treated by YN-01, the mRNA levels of FoxMl and p53have greatly increased, but after48hours the mRNA levels of FoxM1and p53were significantly reduced. In addition, the expression of anti-apoptotic gene Survivin and Bcl-2were significantly reduced after treated by YN-01within48hours. Therefore, it inferred that YN-01may induce HEPG-2to apoptosis by inhibiting the expression of FoxM1and the transcription of its downstream target genes Survivin and Bcl-2.