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Repositioning of cis-flupentixol for the suppression of ovarian cancer cell migration and invasion through ERK5 inhibition
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DOI：10.1186/s10020-026-01592-4.png)
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Abstract
En 中文
Ovarian cancer (OC) remains the most lethal gynecological malignancy, largely because of its late-stage diagnosis and limited effective screening modalities. Despite therapeutic advances, high relapse rates and therapeutic resistance—particularly in metastatic disease—underscore the urgent need for novel therapeutic strategies targeting OC cell dissemination. In this study, the effects of cis-flupentixol (cis-FP), a typical antipsychotic agent, on OC cell migration and invasion were investigated. The effects of cis-FP on OC cell migration and invasion were evaluated using SKOV3 and OVCAR8 cells. Kinase profiling was performed to identify molecular targets of cis-FP, and mechanistic analyses were subsequently conducted to investigate the signaling pathways potentially associated with its inhibitory effects on OC cell motility. Our results showed that cis-FP significantly inhibited the migration and invasion of SKOV3 and OVCAR8 OC cells in a dose-dependent manner. Kinase profiling identified extracellular signal-regulated kinase 5 (ERK5) as a direct molecular target of cis-FP. Subsequent mechanistic analyses revealed that cis-FP reduced ERK5 autophosphorylation and altered focal adhesion kinase (FAK) phosphorylation, changes that were associated with impaired OC cell motility. These findings demonstrate that cis-FP suppresses OC cell migration and invasion and identify ERK5 as a molecular target of cis-FP. Our results suggest that modulation of ERK5-associated signaling pathways may contribute to the inhibitory effects of cis-FP on OC cell motility.
Keywords:
Ovarian cancer
Migration
Invasion
Cis-flupentixol
ERK5
Focal adhesion kinase (FAK)
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