DT-13 suppresses breast cancer metastasis by modulating PLOD2 in the adipocytes microenvironment

Background: Metastasis is the main cause of death in breast cancer and previous researches have indicated the pivotal role of adipocytes in breast cancer metastasis. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, has been proved to exert potential anti-metastatic effect, the detailed mechanisms have not been well elucidated and the role of DT-13 in modulating adipocyte-breast cancer microenvironment has been given little attention. Purpose: This study aims to explore the mechanisms of DT-13 in inhibiting breast cancer metastasis and whether DT-13 inhibit breast cancer metastasis via modulating the interactions between adipocytes and breast cancer cells. Methods: The cytotoxic effect of DT-13 on breast cancer cell viability was detected by MTT assay. Migration assays was used to conduct the effect of DT-13 on breast cancer cells migration. Orthotopic xenograft tumor model was used to test the effect of DT-13 on breast cancer metastasis. qRT-PCR and Western blot were used to investigate the mechanisms of DT-13 inhibiting breast cancer metastasis. Results: DT-13 inhibited breast cancer cells migration at the concentration without cytotoxicity. Furthermore, DT-13 decreased PLOD2 expression through modulating JAK/STAT3 and PI3K/AKT signaling pathways directly or indirectly in the adipocyte-breast cancer microenvironment. Orthotopic implantation mouse model of breast cancer further confirmed that DT-13 inhibited breast cancer metastasis via downregulating PLOD2 in vivo. Conclusion: DT-13 suppressed breast cancer metastasis via reducing the expression of PLOD2.