Bortezomib sensitizes thyroid cancer to BRAF inhibitor in vitro and in vivo

In this study, BRAFV600E-bearing TC cells were treated with BRAFV600E inhibitor, Vemurafenib alone or in combination with the proteasome inhibitor, Bortezomib. The combination of both drugs showed synergistic effects as evidenced by cell growth inhibition (P < 0.05), increased G2-phase cell cycle arrest and induced apoptosis (P < 0.05). In our TC xenograft model, the combination of Vemurafenib and Bortezomib significantly reduced tumor size (P < 0.05) and expression of the markers of cell growth and proliferation, Ki-67 and cyclin D1 (P < 0.001), when compared to monotherapy. Further analysis demonstrated that treatment with Bortezomib sensitized TC cells to Vemurafenib via mitochondrial dysregulation and apoptosis of TC cells, as evidenced by the increase in the expression of p53, Noxa protein, the loss of mitochondrial membrane potential, cytochrome c release and Poly (ADP-ribose) polymerase cleavage. Our results demonstrate a strong clinical potential for the combination of the Bortezomib and the BRAF inhibitor Vemurafenib as an efficient therapeutic approach for the treatment of TC.

Source: Endocrine-Related Cancer - December 21, 2017 Category: Endocrinology Authors: Tsumagari, K., Abd Elmageed, Z. Y., Sholl, A. B., Green, E. A., Sobti, S., Khan, A. R., Kandil, A., Murad, F., Friedlander, P., Boulares, A. H., Kandil, E. Tags: Research Source Type: research