Ovarian cancer is the most lethal gynecological cancer diagnosis. There is no efficient screening process for ovarian cancers and the average stage of diagnosis is stage III. The most common ovarian cancer diagnosis is epithelial ovarian carcinomas, which constitute for 85-90% of prognosis; of this percent, clear cell ovarian carcinoma (CCOC) represents 5% of incidence. CCOC presents unique pathological features, has poor prognosis and has a high reoccurrence rate after treatment. An overexpression of atypical protein kinase C isoforms (PKC-ζ and PKC-ι/λ) has been observed in various malignant cells lines and are linked to pathways for cellular proliferation and invasion. In this investigation, ovarian cell lines (TOV21G and ES-2) were treated with the atypical PKC-ζ inhibitor ζ-Stat and assayed to determine the effects on proliferation and cellular invasion. These assays included cell counting, WST-1 assay, Western Blot and endpoint polymerase chain reaction. Mouse xenograft experiments were also performed to determine the effects of ζ-Stat on TOV21G xenograft tumor growth in vivo. Our data showed that ζ-Stat decreased the proliferation and cell viability of clear cell carcinoma ovarian cancer cells. In addition, it knocked down the protein expression of PKC-ζ, as well as the protein and mRNA levels of RhoA (Ras homolog Family Member A). Our results also showed that tumor growth in athymic female mice was decreased when treated with ζ-Stat and that mouse body weight was maintained. This suggests that PKC-ζ is a novel target in the carcinogenesis of CCOC and its inhibition by way of ζ-Stat decreased the rate of proliferation, tumor growth and expression of invasive protein pathways.

Citation Format: Tracess Smalley, Rekha Patel, Mildred Acevedo-Duncan. An investigation of the effects of the atypical protein kinase C-ζinhibitor ζ-Stat on clear cell carcinoma ovarian cancer proliferation and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1776.