Phage display screening identifies a novel peptide to suppress ovarian cancer cells in vitro and in vivo in mouse models.

Cong Zhou,Jiali Kang,Wei Wei,Xiaoxia Wang,Wenyan Jiang

doi:10.1186/s12885-015-1891-8

Abstract

BackgroundOvarian cancer is a possibly lethal gynecological malignancy and this study utilized phage display technology to screen and identify peptides that specifically bind to ovarian cancer cells and explored the effects of these peptides on ovarian cancer cells in vitro and in vivo.MethodsThe phage displayed peptide library was used to isolate the peptides binding to and internalizing into the ovarian carcinoma cells. Positive phage clones were characterized with DNA sequencing and bioinformatics analysis and then validated with immunofluorescence. Subsequently, the selected peptides were investigated for their cancer-related functions, including cell adhesion, spreading, motility, and invasion in vitro and in vivo.ResultsPeptide1 read as SWQIGGNwas the positive peptide and showed preferential binding to the target cells. Peptide 1 also inhibited cell proliferation, migration, invasion and adhesion of ovarian cancer HO8910 cells in vitro. In vivo, Peptide 1 led to a lower tumorigenicity of HO8910 cells, which was characterized by the inhibitory effect on tumor growth and metastasis of ovarian cells.ConclusionThese studies demonstrate that the phage display-identified tumor cell-binding peptide was able to control ovarian cancer cell viability, migration, invasion, and adhesion capacity in vitro as well as tumor growth and metastasis in vivo. Future studies will be aimed at evaluating the clinical efficacy of the peptide SWQIGGN in ovarian cancer patients.

Highlights

Ovarian cancer is a possibly lethal gynecological malignancy and this study utilized phage display technology to screen and identify peptides that bind to ovarian cancer cells and explored the effects of these peptides on ovarian cancer cells in vitro and in vivo
Most of ovarian cancer patients are diagnosed at an advanced stage of the disease with evidence of metastasis spreading beyond the ovaries [3] and the relapse rate of early stage ovarian cancer is up to 40 % [4,5,6,7]
The biopanning began with the incubation of the phage display peptide library with both normal and tumor cells, in which normal cells were used to deplete peptides that only bind to normal cells and further incubated with tumor cells for identifying the peptides that only bind to tumor cells

Summary

Introduction

Ovarian cancer is a possibly lethal gynecological malignancy and this study utilized phage display technology to screen and identify peptides that bind to ovarian cancer cells and explored the effects of these peptides on ovarian cancer cells in vitro and in vivo. Previous studies utilized phage display peptide libraries to isolate and identify peptides that bind to cell receptors in a cellspecific manner, and exerted biological effects on the target cells [18,19,20,21]. We aimed to screen and identify peptides that could possess highly specific binding capabilities to human ovarian cancer cells, and to investigate the potential of these selected peptides in terms of the control of ovarian cancer in vitro and in vivo. To the best of our knowledge, this study is the first report of such an approach to identify novel targets for ovarian cancer

Objectives

Methods

Results

Conclusion