ArticleIn vivo (Athens, Greece)
Inhibition of Plasminogen Activator Inhibitor-1 (PAI-1) by Tiplaxtinin Attenuates the Aggressive Phenotype of Vulvar Squamous Cell Carcinoma Cells
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Abstract
BACKGROUND/
aimVulvar squamous cell carcinoma (VSCC), while relatively rare, is associated with significant morbidity. Activation of G-protein coupled estrogen receptor 1 (GPER1), which has a tumor-suppressing effect in VSCC, leads to reduced expression of plasminogen activator inhibitor-1 (PAI-1). PAI-1, a key regulator of the plasminogen activation system, is overexpressed in various cancers and is linked to poor prognosis. Its role and potential as a therapeutic target in VSCC remain poorly explored. This study investigated the effects of the specific PAI-1 inhibitor tiplaxtinin (PAI-039, TPX) on the aggressive behavior of VSCC cells MATERIALS AND
methodsExpression of PAI-1 was verified by western blot. The effects of TPX treatment on viability, proliferation, migration, and invasion of A431 and Cal-39 VSCC cells were assessed using AlamarBlue, crystal violet, gap closure, and Boyden chamber assays, respectively. Apoptosis was examined using the Annexin V/propidium iodide (PI) assay.
resultsBoth VSCC cell lines showed PAI-1 expression. With increasing TPX concentrations, viability and proliferation of the VSCC cells decreased significantly. Cell migration and invasion were both significantly reduced under treatment with the PAI-1 inhibitor. Apoptosis was not significantly induced by TPX.
conclusionPAI-1 inhibitor TPX showed a strong inhibitory effect on VSCC cells, significantly reducing their viability, proliferation, migration and invasive capacity. This compound showed a strong ability to suppress important cell functions associated with cancer progression, making it a promising candidate for VSCC therapy to specifically inhibit growth and spread of VSCC.
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