Abstract A79: A novel small molecule, LLL12B, inhibits STAT3 Phosphorylation and sensitizes ovarian cancer cell to cisplatin and paclitaxel treatment

Abstract

Abstract Constitutive activation of signal transducer and activator of transcription 3 (STAT3) signaling plays an important role in many malignant progressions: cell viability, cell migration, cell growth, chemotherapy resistance, and so on. We developed a nonpeptide small molecule, LLL12B, though structure-based design, which targets STAT3 and was confirmed to inhibit STAT3 phosphorylation (tyrosine 705) and induce apoptosis as indicated by the increases of cleaved caspase-3 in human ovarian cancer cells. LLL12B, also inhibits the cell viability, cell migration, and cell growth in ovarian cancer cells. In addition, LLL12B combined treatment with paclitaxel or cisplatin exhibited greater inhibition of cell viability, cell migration, and cell growth than monotherapy in ovarian cancer cells. Furthermore, LLL12B and paclitaxel or cisplatin combination also showed greater inhibition of cell viability, cell migration, and cell colony than cisplatin and paclitaxel combinational treatment, which is a current ovarian cancer standard care therapy. Also, LLL12B combined with paclitaxel and cisplatin showed greater inhibition of cell viability and cell colony than each combinational treatment of two drugs. In summary, our results indicated that the novel small molecule LLL12B is a potent STAT3 inhibitor in ovarian cancer cells. Our results also indicate that the combinational treatment of LLL12B with cisplatin or/and paclitaxel exhibits potent inhibitory activity in ovarian cancer cells, supporting this drug combination as a potential therapeutic strategy for ovarian cancer. Citation Format: Ruijie Zhang, Xiaozhi Yang, Jiayuh Lin. A novel small molecule, LLL12B, inhibits STAT3 Phosphorylation and sensitizes ovarian cancer cell to cisplatin and paclitaxel treatment [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A79.