Background:
Ruxolitinib is a selective JAK1/2 inhibitor approved by the FDA for myelofibrosis in
2014 and nowadays, comprehensive investigations on the potential of the agent as a targeted therapy for haematological
malignancies are on the rise. In multiple myeloma which is a cancer of plasma cells, the Interleukin-
6/JAK/STAT pathway is emerging as a therapeutic target since the overactivation of the pathway is associated
with poor prognosis.
Objective:
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.
Methods:
Cytotoxic effects of ruxolitinib in ARH-77 and NCI-BL 2171 cells were determined via WST-1 assay.
The autophagy mechanism induced by ruxolitinib measured by detecting autophagosome formation was investigated.
Apoptotic effects of ruxolitinib were analyzed with Annexin V-FITC Detection Kit and flow cytometry.
We performed RT-qPCR to demonstrate the expression changes of the genes in the IL-6/JAK/STAT pathway in
ARH-77 and NCI-BL 2171 cells treated with ruxolitinib.
Results:
We identified the IC50 values of ruxolitinib for ARH-77 and NCI-BL 2171 as 20.03 and 33.9μM at the
72nd hour, respectively. We showed that ruxolitinib induced autophagosome accumulation by 3.45 and 1.70
folds in ARH-77 and NCI-BL 2171 cells compared to the control group, respectively. Treatment with ruxolitinib
decreased the expressions of IL-6, IL-18, JAK2, TYK2, and AKT genes, which play significant roles in MM
pathogenesis.
Conclusion:
All in all, ruxolitinib is a promising agent for the regulation of the IL-6/JAK/STAT pathway and
interferes with the autophagy mechanism in MM.
