A Peptide Derived from Nectin-4 Increases Cisplatin Cytotoxicity in Cell Lines and Cells from Ovarian Cancer...

New approaches to the treatment of women with ovarian cancer are desperately needed, since most women develop resistance to chemotherapy and the 5-year survival rate remains low. The hypothesis guiding this study was that the inhibition of cell adhesion could be used as a novel strategy to increase the chemosensitivity of ovarian cancer cells.

The Nectin-4 peptide N4-P10 was used to inhibit the formation of cell-cell aggregates (spheroids) using cell lines and cells isolated from ovarian cancer patients' ascites. Cell lines were pre-treated with peptide N4-P10 or control scrambled peptides and monitored for spheroid formation with live-cell imaging by digital time-lapse photography. Cells were then tested for the cytotoxicity of the chemotherapeutic agent, cisplatin.

Peptide N4-P10 blocked aggregation in cell lines with different levels of Nectin-4 expression and different spheroid morphologies. The cytotoxicity of cisplatin increased in cells pre-treated with peptide N4-P10. Similarly, when single cells were isolated from the ascites of ovarian cancer patients, peptide N4-P10 blocked cell aggregation and increased the cytotoxicity of cisplatin.

These results suggest that targeting the cell-cell adhesive property of cancer cells could serve as a new approach to augment the cytotoxic effect of chemotherapy and potentially reduce disease recurrence in ovarian cancer patients.