Screening of targeting peptides for highly metastatic human ovarian cancer cells and their effect on the biological behavior of ovarian cancer cells / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effect of short peptides specifically binding to highly metastatic human ovarian cancer HO8910PM cells and their effect on the biological behavior of ovarian cancer cells.</p><p><b>METHODS</b>The phage-displayed peptide library was used to isolate the peptides binding and internalizing into the HO8910PM cells. Positive phage clones were characterized with DNA sequencing and bioinformatics analysis. The positive phage clones specifically bound to HO8910 cells were validated with immunofluorescence detection and enzyme-linked immunosorbent assay (ELISA). Furthermore, selected peptides were investigated for their cancer-related functions, including cell adhesion, spreading, motility, and invasion in vitro and in nude mice in vivo. The apoptotic index was detected by TUNEL assay, and VEGF expression by immunohistochemistry.</p><p><b>RESULTS</b>After 4 rounds of screening, apparent enrichment of phages was observed on the HO8910PM cells. ELISA assay showed that among the randomly selected 20 phage clones, 12 can specifically bind to HO8910PM cells. Immunofluorescence assay also showed that the selected positive phage clones can specifically bind to HO8910PM cells. The adherence test showed that the adherence rates of HO8910PM-peptide20, HO8910PM-peptide16 and HO8910PM cells were 49.0%, 96.8% and 100.0%, respectively. There was a significant difference between the cell adherence rates of HO8910PM-peptide20 and HO8910PM cells (P < 0.05). The peptide20 read as "THRVHLH" was a positive peptide and showed preferential binding to targeted cells. The peptide20 effectively inhibited tumor growth and metastasis in the nude mice, and the positive rates of VEGF protein in the tumor tissue of experimental, negative control and blank mice were 21.2%, 81.4% and 85.7%, respectively, showing that the positive rate of VEGF protein in the experimental group was significantly lower than that in the negative control and blank groups (P < 0.01), and the apoptotic index (AI) of the experimental group was (18.21 ± 2.49)%, significantly higher than the (3.76 ± 1.77)% in the negative control group and the (4.78 ± 1.57)% in the blank group (P < 0.01).</p><p><b>CONCLUSIONS</b>A novel short peptide able to specifically bind to highly metastatic human ovarian cancer cells is successfully screened. It can effectively inhibit the growth, invasion and metastasis of ovarian cancer cells, and provides an ideal vector in targeted drug therapy for ovarian cancer.</p>