Abstract 7461: Inhibitory effects of induction of massive apoptosis (PRIMA-1MET) on tumorigenic chemokines in ovarian cancer cells

Abstract Background/Purpose: Ovarian cancer is the most lethal gynecologic malignancy, with TP53 mutations present in >95% of high-grade serous cases, representing a prime molecular target for therapy. In addition to disrupted p53 signaling, elevated pro-inflammatory chemokines drive tumor progression by enhancing proliferation and distant metastasis. This study investigates the therapeutic potential of PRIMA-1MET, a small-molecule reactivator of mutant p53, to suppress tumorigenic chemokine production in ovarian cancer cells. Methods: OVCAR3 cells (harboring TP53R248Q mutation) were cultured under standard conditions. Cell viability was quantified by MTT assay to determine IC50 values. Protein levels and phosphorylation status were assessed by Western blotting. The transcriptional activity of p53 was measured in cells transiently transfected with p53-responsive luciferase reporter plasmids ± wild-type and mutant p53 expression vectors, followed by measurement of luciferase activity. Chemokine profiling was performed using a Human XL Cytokine Array. Results: PRIMA-1MET reduced OVCAR3 viability in a dose-dependent manner (IC50 ≈ 30 μM), and significantly down-regulated chemokines CXCL1, CXCL8, and CCL20, indicating attenuated pro-inflammatory and pro-metastatic signaling. PRIMA-1MET markedly decreased phosphorylated NF-κB, implicating suppression of this master regulator of chemokine transcription. Consistent with p53 reactivation, PRIMA-1MET enhanced p53-driven luciferase reporter activity while concomitantly inhibiting CXCL8 promoter activity—containing an NF-κB binding site—at both basal and IL-1β-induced levels. Conclusion: PRIMA-1MET restores mutant p53 function and inhibits NF-κB-driven chemokine signaling, thereby restraining ovarian cancer progression and metastasis. These findings highlight its promise as targeted therapy. Citation Format: Audene B. Wilkinson, Deok-Soo Son, . Inhibitory effects of induction of massive apoptosis (PRIMA-1MET) on tumorigenic chemokines in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7461.