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

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.

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.

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.

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.

DT-13 suppressed breast cancer metastasis via reducing the expression of PLOD2.