title: A novel peptide, 9R-P201, strongly inhibits the viability, proliferation and migration of liver cancer HepG2 cells and induces apoptosis by down-regulation of FoxM1 expression.
abstract: Overexpression of FoxM1 was closely related to the proliferation, metastasis, chemo-resistance and poor prognosis of various cancers. FoxM1 was regarded as the Achilles' heel of cancer and a potential target for anti-cancer drug discovery. We previously obtained several high affinity peptides from the phage random library against the DNA binding domain of FoxM1c (FoxM1c-DBD) protein. Here in this paper, we found that 9R-P201, one of the novel peptides, showed stronger inhibition to HepG2 cancer cells than those of DU145, HUVEC and L-02 cells with an IC50of 43.6µg/ml (13.1µM). The peptide was highly effective to liver cancer cells with an IC50for L-02 cells of 2855.9µg/ml. We confirmed that 9R-P201 aggregated in the cell nucleus and the expression of FoxM1 was significantly down-regulated at both transcriptional and translational levels in HepG2 cells, leading to the suppression of cell proliferation, migration, angiogenesis, and induction of apoptosis. Whole genomic RNA sequencing analysis revealed that 357 genes were significantly and differentially expressed, most of them were enriched in cancer-associated biological processes. Finally, treatment of HepG2 xenografts with 9R-P201 resulted in growth inhibition and down-regulation of foxM1 expression in tumors. Collectively, our findings suggested that 9R-P201 could strongly inhibit the viability, proliferation and migration of liver cancer HepG2 cells and induce apoptosis by down-regulation of FoxM1 and regulation of related gene expression in signal transduction passways. Thus, 9R-P201 holds great potential as a lead anti-cancer drug targeting FoxM1.
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Zhenfei
authors.initials: Z
authors.lastname: Bi
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Ruofang
authors.initials: R
authors.lastname: Ding
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Rongkun
authors.initials: R
authors.lastname: Dou
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China. Electronic address: zhiyunguo@gmail.com.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Laboratory of Molecular Evolution and Applied Biology, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan 610031, China. Electronic address: maocq@home.swjtu.edu.cn.
authors.forename: Canquan
authors.initials: C
authors.lastname: Mao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C000617772:9R-P201; D000970:Antineoplastic Agents; D000072278:Forkhead Box Protein M1; D010455:Peptides
keywords: 9R-P201; Apoptosis; FoxM1-DBD; HepG2 cells; Viability