化疗耐药上皮性卵巢癌（EOC）预后不良，促使人们寻找新的治疗药物。用于治疗精神分裂症的二苯基丁基哌啶 (DPBP) 类抗精神病药物已显示出抗癌作用。本研究旨在利用 EOC 的体外和体内模型研究五氟利多、氟螺林和匹莫齐特 (DPBP) 的临床前疗效。人 EOC 细胞系 A2780、HeyA8、SKOV3ip1、A2780-CP20、HeyA8-MDR 和 SKOV3-TR用五氟利多、氟螺哌啶和匹莫齐特治疗，并评估细胞增殖、凋亡和迁移。还使用体内小鼠模型研究了 DPBP 的临床前疗效，包括 EOC 的细胞系和患者来源的异种移植物 (PDX)。DPBP 药物显着降低化疗敏感（A2780、HeyA8 和 SKOV3ip1）和化疗耐药（A2780-CP20）的细胞增殖、HeyA8-MDR 和 SKOV3-TR）细胞系。其中五氟利多对所有细胞系均具有较强的细胞毒作用。 Penfluridol 显着增加 EOC 细胞的凋亡并抑制其迁移。在HeyA8细胞系异种移植小鼠模型中，与对照组相比，五氟利多组的肿瘤重量显着降低。在 HeyA8-MDR 紫杉醇耐药模型中，与紫杉醇组或对照组相比，五氟利多组的肿瘤重量显着降低。 Penfluridol对PDX模型具有抗癌作用。Penfluridol对EOC细胞和异种移植模型（包括PDX）具有显着的抗癌作用。因此，五氟利多疗法作为一种药物再利用策略，可能是 EOC 的潜在治疗方法。© 2025。亚洲妇科肿瘤学会、韩国妇科肿瘤学会和日本妇科肿瘤学会。

Chemoresistant-epithelial ovarian cancer (EOC) has a poor prognosis, prompting the search for new therapeutic drugs. The diphenylbutylpiperidine (DPBP) class of antipsychotic drugs used in schizophrenia has shown anticancer effects. This study aimed to investigate the preclinical efficacy of penfluridol, fluspirilene, and pimozide (DPBP) using in vitro and in vivo models of EOC.Human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with penfluridol, fluspirilene, and pimozide, and cell proliferation, apoptosis, and migration were assessed. The preclinical efficacy of DPBP was also investigated using in vivo mouse models, including cell lines and patient-derived xenografts (PDX) of EOC.DPBP drugs significantly decreased cell proliferation in chemosensitive (A2780, HeyA8, and SKOV3ip1) and chemoresistant (A2780-CP20, HeyA8-MDR, and SKOV3-TR) cell lines. Among these drugs, penfluridol exerted a relatively stronger cytotoxic effect on all cell lines. Penfluridol significantly increased apoptosis and inhibited migration of EOC cells. In the cell line xenograft mouse model with HeyA8, the penfluridol group showed significantly decreased tumor weight compared with the control group. In the paclitaxel-resistant model with HeyA8-MDR, the penfluridol group had significantly decreased tumor weight compared with the paclitaxel or control groups. Penfluridol exerted anticancer effects on the PDX model.Penfluridol exerted significant anticancer effects on EOC cells and xenograft models, including PDX. Thus, penfluridol therapy, as a drug repurposing strategy, might be a potential therapeutic for EOCs.© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.