Abstract 2678: LLL12B, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer cells

Abstract Persistent STAT3 signaling has been recognized as a cancer therapeutic target in some cancer types including triple-negative breast cancer, and the development of effective small molecule STAT3 inhibitors for potential cancer therapy is desirable. In this study, we tested a novel oral bioavailable small molecule STAT3 inhibitor, LLL12B in MDA-MB-231, SUM159, and 4T1 triple-negative breast cancer cells. Triple-negative breast cancer cells frequently express persistent STAT3 phosphorylation and its cell viability is sensitive to STAT3 knockdown by siRNA. LLL12B selectively inhibited IL-6 mediated induction of STAT3 phosphorylation but had little effect on IFN-γ mediated induction of STAT1 phosphorylation or EGF mediated induction of ERK phosphorylation. LLL12B inhibited STAT3 phosphorylation, induced cell apoptosis, and reduced cell colony formation in triple-negative breast cancer cells. In addition, LLL12B inhibited cell migration of triple-negative breast cancer cells. Furthermore, LLL12B suppressed tumor growth of MDA-MB-231 triple-negative breast cancer cells in a mammary fat pad syngeneic mouse model. Together, our findings suggest that targeting persistent STAT3 signaling pathway by novel small molecule LLL12B may be a potential approach for triple-negative breast cancer therapy. Citation Format: Li Pan, Xiang Chen, Feyruz V. Rassool, Chenglong Li, Jiayuh Lin. LLL12B, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2678.