Inhibition of Plasminogen Activator Inhibitor-1 (PAI-1) by Tiplaxtinin Reduces Aggressiveness of Cervical Carcinoma Cells

Abstract

Background/aim: The effect of G-protein-coupled estrogen receptor 1 (GPER1) on tumors depends on tumor entity, with its expression level influencing signal transduction and function. Recent research suggests that GPER1 promotes tumor suppression in cervical carcinoma (CC). In contrast, silencing GPER1 increases expression of serpin family E member 1 (SERPINE1) and its protein, plasminogen activator inhibitor-1 (PAI-1), and promotes tumor progression, raising the question of whether PAI-1 might be a suitable target for the treatment of CC. To explore this, we examined the impact of PAI-1 inhibition using Tiplaxtinin (PAI-039, TPX).

Materials and methods: The effects of TPX treatment on viability, colony formation, migration, and invasion of SiHa cervical squamous cell carcinoma (CSCC) and HeLa cervical adenocarcinoma (CAC) cells were assessed using AlamarBlue, colony formation, gap closure, and Boyden chamber assays, respectively. Apoptosis was examined using the Annexin/PI assay, while the cell cycle was analyzed in more detail using the PI assay.

Results: With increasing TPX concentration, viability and colony formation of SiHa and HeLa cells decreased significantly. Cell migration was strongly reduced under PAI-1 inhibitor treatment, while invasion showed a slight decline. Apoptosis and cell cycle were only minimally affected by TPX.

Conclusion: PAI-1 inhibitor TPX showed a strong inhibitory effect on both SiHa CSCC and HeLa CAC cells, significantly reducing their viability, colony formation, and migratory capacity. The observed effects suggest that TPX could potentially be used to target and hinder the growth and spread of both CSCC and CAC cells.

Keywords: Cervical carcinoma (CC); G-protein-coupled estrogen receptor 1 (GPER1); Tiplaxtinin; inhibitor; plasminogen activator inhibitor-1 (PAI-1); serpin family E member 1 (SERPINE1).