Breast cancer organoid model allowed to reveal potentially beneficial combinations of 3,3′-diindolylmethane and chemotherapy drugs

Epigenetic alterations represent promising therapeutic targets in cancer treatment. Recently it was revealed that small molecules have the potential to act as microRNA silencers. Capacity to bind the discrete stem-looped structure of pre-miR-21 and prevent its maturation opens opportunities to utilize such compounds for the prevention of initiation, progression, and chemoresistance of cancer. Molecular simulations performed earlier identified 3,3′-diindolylmethane (DIM) as a potent microRNA-21 antagonist. However, data on DIM and microRNA-21 interplay is controversial, which may be caused by the limitations of the cell lines. •A tumor organoid culture from metastatic breast cancer was established.•Histological analysis and IHC confirmed that organoids share morphologic and molecular features with the primary tumor.•FACS and cytogenetic analysis confirmed that organoids possess unique molecular characteristics.•DIM increases susceptibility of organoids to methotrexate and cyclophosphamide treatment.