Targeting Wnt Signal Pathway In The Treatment Of Multiple Myeloma

To explore the possibility of targeting Wnt pathway in the treatment of multiple myeloma, we first examined the sensitivity of different myeloma cell lines to Bortezomib and protein levels ofβ-catenin to find their relationship; Secondly , myeloma cells were treated with Bortezomib, arsenic trioxide (AS2O3) or 2-methoxyestradiol (2ME2). Typan blue dye exclusion and modified MTT were used to assess the cell viability,while Annexin V-FITC and PI staining with flow cytometry was performed to examine the apoptosis rate. RT-PCR was used to detectβ-catenin mRNA, and western blot to detect the protein. To compare the difference of LRP6 in myeloma cells and mesenchymal stem cells (MSC), myeloma cell lines, fresh myeloma cells and MSC from MM patients were cultured in vitro. The different domains of LRP6 which Wnt or DKK-1 binds with were examined through RT-PCR. Our study showed that the protein levels of beta-catenin were negatively associated with the sensitivity of myeloma cell lines to Bortezomib, AS2O3 and 2ME2 enhanced the anti-MM activity of Bortezomib, and RT-PCR showed different expression levels of Wnt and DKK-1 binding domains in tested cells.