Boylan Kristin L M, Walz Caitlin, Schefter Alexandra M, Skubitz Amy P N
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Ovarian Cancer Early Detection Program, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2025 Mar 6;17(5):901. doi: 10.3390/cancers17050901.
BACKGROUND/OBJECTIVES: 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.
背景/目的：由于大多数女性会对化疗产生耐药性且5年生存率仍然较低，因此迫切需要治疗卵巢癌女性患者的新方法。本研究的指导假设是，抑制细胞黏附可作为一种增加卵巢癌细胞化疗敏感性的新策略。
使用Nectin-4肽N4-P10，通过细胞系和从卵巢癌患者腹水中分离出的细胞来抑制细胞-细胞聚集体（球体）的形成。细胞系先用肽N4-P10或对照乱序肽进行预处理，然后通过数字延时摄影的活细胞成像监测球体形成。随后检测细胞对化疗药物顺铂的细胞毒性。
肽N4-P10在具有不同Nectin-4表达水平和不同球体形态的细胞系中均能阻止聚集。用肽N4-P10预处理的细胞中顺铂的细胞毒性增加。同样，当从卵巢癌患者腹水中分离出单细胞时，肽N4-P10可阻止细胞聚集并增加顺铂的细胞毒性。
这些结果表明，针对癌细胞的细胞-细胞黏附特性可能是增强化疗细胞毒性作用并潜在降低卵巢癌患者疾病复发的一种新方法。
