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. Methods: 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. Results: 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. Conclusions: 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：由于大多数卵巢癌患者对化疗产生耐药性且五年生存率持续偏低，亟需探索治疗新策略。本研究假设抑制细胞黏附可作为增强卵巢癌细胞化疗敏感性的创新途径。方法：采用Nectin-4多肽N4-P10，通过卵巢癌细胞系及患者腹水分离细胞，抑制细胞间聚集体（球体）形成。使用数字延时摄影技术进行活细胞成像，监测经N4-P10多肽或对照乱序多肽预处理的细胞系球体形成情况，随后检测化疗药物顺铂的细胞毒性。结果：N4-P10多肽能有效阻断不同Nectin-4表达水平及不同球体形态的细胞系聚集。经该多肽预处理的细胞对顺铂的敏感性显著增强。同样，在卵巢癌患者腹水分离的单细胞中，N4-P10多肽既可抑制细胞聚集，又能增强顺铂的细胞毒性。结论：靶向癌细胞的细胞间黏附特性可作为增强化疗细胞毒性、潜在降低卵巢癌患者疾病复发的新策略。
肿瘤(癌症)患者之家