LAUSR

Leiomyoma (LM) and leiomyosarcoma (LMS) are uterine mesenchymal tumors that present variable clinical and biological behavior. They are associated with infertility, pelvic pain and abnormal uterine bleeding.. LM is a benign tumor commonly affecting women at reproductive age whereas LMS represents 40% of all uterine sarcomas. These tumors do not have specific therapy and their origin is still uncertain. Some researchers believe that degenerated LM may to turn to LMS. FOXO3a, a transcriptional factor, has been associated to regulation of several cellular functions as well as tumors development. Previously, we detected that FOXO3a gene and protein expression present different expression profiles in LM and LMS. In this current study, our aim was to investigate the in vitro effects of metformin and genistein, both inhibitors of AKT-mediated FOXO3a phosphorylation, treatment in LM and LMS cells behavior. LM (THESCs CRL-4003) and LMS (SK-UT-1) cell lines were grown in specific mediums and conditions (ATCC recommendations), and treated with different drugs concentrations (0.1 - 200 uM and 0.1 - 200 nM, for metformin and genistein, respectively) at several time points (0, 24, 48, 72, 96 and 120 h). After treatment, cells were evaluated for gene and protein expression, cell proliferation, migration and apoptosis. Gene expression was assessed by quantitative Real Time PCR and proteins were evaluated by immunocitochemical analysis. Genistein depicted high toxicity for the cells, due to its vehicle (DMSO), in all tested dose and times. Metformin presented higher efficiency in cell proliferation and migration inhibition for both cell lines, as well as in the apoptosis induction. Prominent effects were observed in LMS cells after treatment with 25 uM for 72h. Gene expression analysis showed a slight decrease in FOXO3a expression after treatment with these drugs. Our results suggest that treatment with metformin induces the FOXO3a function restoration in the cells, by inhibition of the AKT/PI3K pathway, and can represent a future alternative target therapy for these neoplasias. Citation Format: Anamaria R. Ricci, Giovana D. Maffazioli, Edmund C. Baracat, Katia C. Carvalho. Metformin treatment inhibits uterine leiomyoma and leiomyosarcoma cells growth and migration in vitro [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4027.