Inflammasome activation contributes to cisplatin resistance in ovarian cancer

Epithelial ovarian cancer (EOC) is an alarming malignancy with frequent relapse and resistance to chemotherapy. Understanding the mechanism related to these phenotypes is urgent. Here, we investigated the roles of inflammasomes, NLRP1 and NLRP3, and pyroptosis in EOC progression and resistance to treatment.

Cell viability under cisplatin (CDDP) treatment was measured with diphenyltetrazolium bromide (MTT), and the IC50 values were calculated for the A2780, ACRP, and OVCAR3 cell lines. The levels of cytokines (interleukin-1β, IL-6, and TNFα) present in the supernatant were measured via ELISA. Caspase-1 activation was detected through the Caspase-Glo® 1 Assay. The cell death profile was determined via flow cytometry using Annexin V/PI staining, and the formation of pores in the cell membrane was measured using PI. A wound healing assay was used to investigate the effects of treatment with CDDP combined with a caspase-1 inhibitor (Ac-YVAD-CHO) on cell migration.

IC50 values indicate increasing CDDP resistance across the following cell lines: A2780 (10.41 μM), ACRP (35.92 μM), and OVCAR3 (43.52 μM). Cytokine secretion and Caspase-1 activation were greater in treated cells than in untreated cells. CDDP-treated cells exhibited increased lytic cell death and pore formation. Caspase-1 inhibition during treatment with CDDP reduced wound closure, indicating reduced cell migration.

Our findings suggest that inflammasome activation and pyroptosis are mechanisms associated with ovarian cancer chemoresistance to CDDP, contributing to the devastating scenario of this disease. Targeting the NLRP1 and NLRP3 pathways could represent a promising strategy to improve OC treatment.