Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib.

Beta-catenin, the key protein in canonical Wingless/int (Wnt) pathway, degrades via ubiquitin-proteasome pathway. Recently, it proved important roles in the proliferation of myeloma cells. But little is known about whether cytoplasmic beta-catenin content is associated with myeloma cell's sensitivity to Bortezomib. We examined the constitutive expression of beta-catenin in five myeloma cell lines and primary cells from patients. Meanwhile, the effect of Bortezomib combined with arsenic trioxide (As(2)O(3))/2-methoxyestradiol (2ME2) on beta-catenin accumulation, myeloma cells' survival, apoptosis and their sensitivity to Bortezomib were also investigated. Our study proved that beta-catenin protein levels are negatively associated with myeloma cells' sensitivity to Bortezomib. As(2)O(3)/2ME2 can reduce cytoplasmic beta-catenin accumulation after proteasome inhibition and enhance myeloma cells' sensitivity to Bortezomib. This will preliminarily help to optimize the new therapeutic regimens for MM treatment in the future.