In vitro application of ruxolitinib in multiple myeloma treatment
Project no. 159 · Status: Kapanmış · 2018
Summary
Ruxolitinib is a selective JAK1/2 inhibitor approved by FDA for myelofibrosis in 2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for hematological malignancies are on the rise. In multiple myeloma, IL6/JAK/STAT pathway is emerging as a therapeutic target since the over activation of the pathway is associated with poor prognosis. In this study, our purpose was to discover the potential anticancer effects of ruxolitinib in ARH-77 multiple myeloma cell line compared to NCI-BL 2171 human healthy B lymphocyte cell line. We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9 µM at the 72th hour, respectively. Investigation of the autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70 folds in ARH-77 and NCI-BL 2171 cells compared to control group, respectively. We performed RT-qPCR to demonstrate the expression changes of the genes in IL-6/JAK/STAT pathway in ARH-77 and NCI-BL 2171 cells treated with ruxolitinib. Treatment with ruxolitinib decreased the expressions of IL6, IL18, JAK2, TYK2 and, AKT genes which play significant roles in MM pathogenesis. All in all, ruxolitinib is a promising agent in regulating IL6/JAK/STAT pathway and interfering with autophagy mechanism in multiple myeloma.